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PATHOLOGY

 

OF LABORATORY MICE

 

 

 

 

Stephen W. Barthold, D.V.M, Ph.D.

 

Professor and Director

Center for Comparative Medicine

Schools of Medicine and Veterinary Medicine

University of California, Davis

One Shields Ave.

Davis, CA  95616

 

swbarthold@ucdavis.edu

(530) 752-1245

 

Director

UC Davis Mouse Biology Program

http://mouse.ucdavis.edu/

(530) 754-MOUSE

mbp@ucdavis.edu

 

 

 

 

 

 

 


 

THE LABORATORY MOUSE

 

Mus musculus sensu  lato

 

(Mus domesticus, castaneus, musculus, et al.)

 

 

Normal features:

 

Social structure: 

            Deme – dominance heirarchy allows mature males to exist within the population (unusual for rodents)

            Pheromones

Physiology:

            Heterothermic: not quite homeothermic, not quite poikilothermic. Wide adaptive environmental range, but intolerant to sudden temperature variations. Death @ >80 degrees F if sudden.

Digestive system:

Incisive foramen

Continuously growing incisors, rooted molars

Gastric yeast (Torulopsis spp.)

Simple intestine

Sexual dimorphism of submaxillary salivary gland serous cells

Paneth cells in crypts - very prominent granules

Ileal filamentous bacteria

Absorption vacuoles in infant small intestine

Physiologic hyperplasia in lactating, pregnant females

Very short rectum -  descending colon enveloped in serosa almost to anus, thereby making mouse susceptible to rectal prolapse

Variable liver lobation

Certain strains (BALB) prone to normal background hepatocellular fatty change. Exacerbated in disease.

Hepatocellular polykarya, megalokarya (polyploidy)

Hepatocellular intranuclear cytoplasmic invagination

Giant pancreatic islets

Hyalinosis and crystals in biliary and gall bladder epithelium (B6, 129)

Respiratory system:

Obligate nasal breathers

Prominent vomeronasal organs

Single left lung lobe, four right lobes.

No intrapulmonary bronchi (no cartilage)

Cardiac muscle extends around large pulmonary veins

Hyalinosis in respiratory, especially nasal epithelium (B6, 129); crystals in lung

Hematopoeitic / lymphoid system:

Extramedullary hematopoeisis in liver, spleen (sometimes adrenal) in infant mice through weaning age. Continues in spleen throughout life, particularly in pregnancy. Disease states readily induce EMH in liver of adults.

No tonsils

Thymus does not completely involute

Indistinct Hassel’s corpuscles in thymus

Ectopic thymus in thyroid, parathyroid and parathyroid in thymus

Accessory spleens

“Patches” of lymphoid cells on visceral pleura of lung, peritoneum (B1 cells)

Mast cells can be common in spleen of some strains (i.e. A)

Peyer’s patches in both small and large intestine

Short life span of erythrocytes (42 days compared to approx. 100 in humans), resulting in anisocytosis, polychromasia, Howell-Jolly bodies

Peripheral blood granulocytosis in adult males

“Doughnut” granulocytes, or ring forms especially in tissues

Hemosiderin pigment accumulates in spleen, particularly multiparous females

Endocrine system:

Accessory adrenals common

No discernable zona reticularis

X zone: basophilic cells surrounding medulla around 10 days of age, then disappear as mice mature.  Swollen, pigmented residual cells

Adrenal subcapsular spindle cells

Epithelial-lined cysts in thyroid

Genitourinary system:

Females have large “genital papillus” (clitoris) with urethral opening near end

Single renal papillus extends into upper ureter

Sexual dimorphism of Bowman’s capsular epithelium

Numerous glomeruli/volume of cortex

Copulatory plug - agonal event. Often found in urinary bladder, urethra as incidental finding, but can cause antemortem obstruction (obstructive uropathy)

Redundant testes that are freely retractable into abdomen

Proteinuria in adult males

Mouse urinary protein highly antigenic. Produced in liver, excreted in copious amounts (pheromone signaling)

Prominent accessory sex glands: prepucial glands, seminal vesicles

Skeletal:

No Haversian bone

Open (but inactive) epiphyses in many long bones of adults

Hematopoeisis remains active in long bones throughout life

Cardiovascular:

Bone/cartilage at aortic root - variable, and usually cartilagenous

Misc.

Melanosis in B6 mice - meninges of olfactory bulbs, optic nerves, heart valves, endothelium of aorta, parathyroids, capsule and trabeculae of spleen

 

 


Spontaneous (non-infectious) Diseases

 

Amyloidosis

 

Amyloid is extracellular fibrillar protein with a high content of beta-pleated sheets that is deposited extracellularly in various tissues.  Two types of amyloid occur in mice: AA, and AapoAII. AA amyloid is associated with an increase in serum precursor apoSAA, which is induced in hepatocytes in response to cytokines produced during inflammatory and neoplastic disease. AA fibril formation and deposition involves partial degradation of apoSAA by macrophages. AA amyloidosis can be induced with repeated injections of casein and other inflammatory stimuli (therefore also referred to as secondary amyloidosis).  AapoAII amyloid deposits consist of intact apoAII proteins (no degradation). The precursor, apoAII, is also produced by the liver (also termed primary amyloidosis).  Naturally occurring amyloidosis in aging mice generally consists of a mixture of AA and AapoAII amyloid.  AA amyloid tends to be deposited in spleen, liver, kidneys, and many other organs.  AapoAII amyloid tends to be less severe in liver and spleen, with more deposition in adrenals, intestine, heart, lungs, thyroid, ovaries and testes.  In spite of these features, the patterns of amyloid deposition varies markedly among different genotypes of mice. Difficult to distinguish primary from secondary amyloidosis, but secondary (due to inflammatory disease) tends to prefer liver and spleen, whereas these sites are minimally involved with primary amyloidosis. Chronic antigenic exposure of infectious and parasitic (especially mites) disease accelerates amyloidosis, with earlier onset in strains like B6.   

 

Amyloidosis is a singularly important spontaneous disease of mice.  It is common in both domestic and wild mice. High prevalence and early onset of AapoII amyloidosis in A, SJL; high prevalence, late onset of amyloidosis (probably mixed amyloid) in B6 and B10 mice; rare in BALB, C3H, DBA. Common in aging Swiss mice, which are prone to AapoII amyloidosis. More common in male mice due to fighting.  Tissue distribution patterns vary by genotype, but most frequent sites are renal glomeruli, renal interstitium, lamina propria of small and large intestine, myocardium, parotid salivary gland, thyroid, adrenal cortex, perifollicular areas of spleen, pulmonary alveolar septa, periportal liver, tongue, testis, ovary, myometrium, aorta, pancreas, etc. Associated with cardiac atrial thrombosis, renal papillary necrosis.  Deposition of amyloid-like hyaline material is common in nasal submucosa near the ventral septum, but does not stain with Congo Red.  Looks like amyloid, but biochemical composition has not been determined.  Tumor-associated amyloid is also seen, particularly bronchioloalveolar adenomas in BALB (which seldom develop multisystemic amyloidosis). Localized amyloid in corpora lutea in CBA and DBA.  Congo Red/polarized light variable result: works well in some tissues, poorly in others of same mouse.

 

Dehydration:

Mice require large amounts of water. Dehydrate rapidly when water bottle or automatic water is not functional. Death within 24 hours.

Hypothermia /hyperthermia:

Mice susceptible to sudden extremes in temperature. More commonly, water bottle accidents flood cage, making mice wet, hypothermic. High mortality.

Integument:

Barbering:            genotype-specific patterns

Trichotillomania:  genotype-specific (B6)

Pugilism:             genotype-specific patterns (male BALBs)

Nasal alopecia:    barbering, trichotillomania, or mechanical abrasion

Ringtail:               low humidity, preweanling mice.

Gangrene:            low humidity, cold air in hairless mice. Cotton bedding infants

Nervous system:

Hydrocephalus (B6 mice)

Hypoplasia/aplasia of corpus callosum (incomplete penetrance, ca. 70% in 129, BALB.

            Incidence higher in litters born to lactating dams.

Brain sand

Vacuolation of neuropil (aging artifact)

Retinal degeneration: common in C3H, CBA and Swiss; A, AKR, BALB, C57BL and DBA normal. Seen in wild mice. Multigenic, but usually begins prior to weaning and is nearly complete by weaning.

            Microophthalmia in Black mice (B6, B10, etc.) typically unilateral

            Laminar necrosis of neurons in FVB mice due to seizures

Reyes-like syndrome: high morbidity and mortality among BALB/cBy-types

Gastrointestinal:

Malocclusion, incisor overgrowth

Tooth decay: acidified water

Foreign body gingivitis

Gastric mucosal hyperplasia in immunodeficient mice

Salivary ductal cysts

Duodenal and pyloric stress ulcers

Mesenteric disease in aged mice: enlarged, atrophic mesenteric lymph nodes

Eosinophilic secretory inclusions in biliary and gall bladder epithelium (B6)

Adynamic ileus associated with i.p. Avidin (chloral hydrate) anesthetic     

Respiratory:

Crystal pneumonia in B6, motheaten (B6 mutant) and 129 mice

Eosinophilic secretory inclusions (hyalinosis) in respiratory epithelium (B6, 129)

Nasal obstruction - bedding

Inhalation pneumonia - bedding, food

Hematopoeitic / lymphoid:

Periarterial and periductal lymphocytic infiltrates: salivary gland, lung, kidney, etc.

Genitourinary:

Obstructive uropathy due to copulatory plugs

Glomerular hyalinosis (basement membrane thickening) in aged mice (AKR, BALB, CBA)

Glomerulonephritis in some strains, like NZBNZWF1, BALB

Glomerular amyloidosis and interstitial amyloidosis

Hydronephrosis

Polycystic kidneys (BALB)

Chloroform toxicity: exquisite susceptibility of DBA, C3H

Hyaline droplets in tubular epithelium associated with histiocytic sarcoma

Arteritis/segmental infarction

Megalokaryosis in male ductal epithelium of aged mice

Muco(hydro)metra:  imperforate vagina

Cystic endometrial hyperplasia

Enlarged seminal vesicles in B6 mice

Musculoskeletal:

Sternal necrosis

Fibro-osseous proliferation (female mice)

Skeletal muscle mineralization (C3H)

Cardiovascular:

Atrial thrombosis (see amyloidosis)

Epicardial mineralization (BALB, DBA)

Myocardial mineralization (C3H)

Idiopathic polyarteritis: segmental infarcts in kidneys, vestibular disease, coronary artery, ovary

Misc.

Obesity: central pattern

Pregnancy toxemia: rare. BALB

 

Neoplasia

 

Lymphoid / myeloid tumors. Retroviruses (both MuLV and MMTV) significant factor

AKR:      thymic

BALB:    peripheral lymph nodes, generalized

SJL:      mesenteric nodes, generalized

Mammary tumors. Retroviruses significant factor

C3H:   high prevalence

BALB, C57BL: low prevalence

Bronchioloalveolar adenomas: BALB, A, CR common. C57BL rare.

Trichoepitheliomas

Hepatocellular tumors: DBA, A strain common

Eosinophilic, basophilic, clear cell foci are considered “preneoplastic”

Harderian gland adenomas/carcinomas

Myoepitheliomas

Common in BALB. 

Submaxillary and parotid salivary glands, but also mammary, prepucial and Harderian. Concomitant myeloid hyperplasia.

Misc:

Islet cell tumors

Pituitary adenomas (FVB mice)

Zymbal gland tumors

Sarcomas (lymphangio, fibro, myo, osteo, etc.): transgenic mice

Teratomas (129 and KO mice)

 

 

PSEUDOPATHOGENS

 

 

Esophageal G+ cocci

Gastric yeast (Torulopsis spp.)

Ileal filamentous bacteria

Entameba muris

Tritrichomonas muris


 

INFECTIOUS AGENTS OF MICE

 

 

2.    VIRUSES

 

                  A.  DNA
                        Adenovirus                    MAd-1 (FL), MAd-2 (K87)

                        Herpesvirus                   mouse cytomegalovirus (MCMV)
                                                            mouse thymic virus (MTV)

                        Papovavirus                   K virus
                                                            polyoma virus

                        Parvovirus                     minute virus of mice (MVM)
                                                            mouse parvovirus (MPV)

                        Poxvirus                        ectromelia virus

 

                  B.   RNA
                        Arenavirus                     lymphocytic choriomeningitis virus (LCMV)

                        Arterivirus                      lactate dehydrogenase–elevating virus (LDV)

                        Bunyavirus                    hanta-like virus

                        Calicivirus                     murine norovirus (MNV-1)           

                        Coronavirus                   mouse hepatitis virus (MHV)

                        Paramyxovirus               pneumonia virus of mice (PVM)
                                                            Sendai virus

                        Picornavirus                  mouse encephalomyelitis virus (MEV)

                        Reovirus                        epizootic diarrhea of infant mice (EDIM) virus
                                                            reovirus 1, 2, 3

                        Retrovirus                      murine leukemia virus (MuLV)
                                                            murine mammary tumor virus (MMTV)

 

 

Adenoviridae

    Murine Adenovirus 1 and 2

    MAd- 1 (FL)

    MAd-2 (K87)

 

1.   Prevalence: MAd-1 rare or nonexistent in laboratory mice. MAd-2 moderate.

2.   Diagnosis: Serology, lesions (intranuclear inclusions)

3.   Disease: MAd-1 (FL, ala Friend leukemia) causes multisystemic infection with viruria in young and immunodeficient mice. Lethal in suckling and SCID mice. Subclinical in older mice, including athymic nude mice. Type A intranuclear inclusions, especially in renal tubules, adrenal cortex. Animal model for adrenal necrosis. Infection of SCID and nude mice associated with enteritis, inclusions in enterocytes. Intestinal component has not been carefully examined. MAd-2 (K87) is strictly enterotropic and less virulent, even in infant and immunodefieient mice. Inclusions in enterocytes. Usually subclinical, but can cause runting and low mortality in suckling mice.

4.   Transmission: nose, urine, feces.

5.   Duration: acute to chronic

6.   Comment: MAd-1 probably extinct. MAd-1 antigen does not cross-react with MAd-2 antibody, but MAd-2 antigen will react with MAd-1 antibody.

 

Herpesviridae

    Murine Cytomegalovirus (MCMV); Murid Herpesvirus 1 (MuHV-1)

 

1.   Prevalence: rare in laboratory mice; common in wild mice.

2.   Diagnosis: serology (not generally used); salivary gland lesions

3.   Disease: Natural infections and experimental infections in adult immunocompetent mice are subclinical and limited to salivary glands. Submaxillary glands preferentially involved, with intranuclear and intracytoplasmic inclusions in tubular epithelium and nonsuppurative interstitial inflammation. Disseminated infection in experimentally inoculated infant mice and immunosuppressed mice, including SCID mice.

4.   Transmission: saliva, tears, urine. In utero transmission rare, even in experimentally inoculated mice.

5.   Duration: chronic and latent (only latent virus of mice)

6.   Comment: Subfamily Beta-herpesvirinae, Genus Muromegalovirus. Studied as model for human disease, but does not mimic human disease or vertical transmission very well.

 

Herpesviridae

    Mouse Thymic Virus (MTV); Murid herpesvirus 3 (MuHV-3); thymic necrosis virus; thymic agent

 

1.   Prevalence: nonexistent or rare in laboratory mice; common in wild mice

2.   Diagnosis: serology (not generally used); mouse bioassay (thymic necrosis in neonates)

3.   Disease: Natural infection and infection in adult mice subclinical. Experimental inoculation of neonates causes thymic necrosis and generalized lymphoid (T cell) necrosis, with intranuclear inclusions. Infection of older mice largely restricted to salivary glands, but no lesions.

4.   Transmission: saliva.

5.   Duration: chronic

6.   Comment: Unclassified herpesvirus. Because of salivary tropism, MTV (not to be confused with MTV of mammary tumor virus) is a frequent contaminant of MCMV stocks. International Union of Microbiological Societies 2000 has renamed the virus MuHV-3, which further confuses with MHV-3. Furthermore, MuHV-2 is not even a herpesvirus of mice, but rather voles!

 

Papovaviridae

    K Virus; Murine Pneumotropic Virus (MPtV)

 

1.   Prevalence: rare or nonexistent

2.   Diagnosis: serology

3.   Disease: Subclinical in adult mice. Necrosis, intranuclear inclusions in endothelial cells of villus lamina propria. Neonates develop viremic dissemination to pulmonary and hepatic vascular fields. Pulmonary endothelial damage with hemorrhage, edema, death. Viremia blocked in older mice by early neutralizing antibody response.

4.   Transmission: fecal

5.   Duration: acute to chronic

6.   Comment: Polyomavirus Genus of Papovaviridae.  Primary site of virus excretion is renal tubules, with minimal lesions. Therefore, biologically similar to other polyomaviruses.  Due to rarity of this virus, natural infection of immunodeficient mice has not been reported, but consequences can be predicted.  International Union of Microbiological Societies 2000 has renamed the virus MPtV, even though the virus is not primarily pneumotropic!

 

Papovaviridae

    Polyoma Virus; Murine Polyomavirus (MPyV);  parotid tumor agent; salivary gland tumor virus

 

1.   Prevalence: rare as natural infection in laboratory mice. Common in wild mice.

2.   Diagnosis: serology

3.   Disease: Usually subclinical. Experimental inoculation of neonates with high doses of oncogenic strains results in multisystemic infection, followed by multiple hyperplastic and neoplastic foci in a variety of tissues (poly-oma). Natural infection in young mice multisystemic, but tumors are exceedingly unlikely. Renal tubules important target with viruria, as with many polyomaviruses of other species. Mild necrosis, inclusions, interstitial inflammation. Older mice clear infection rapidly, with no virus shedding. Natural and experimental infection of athymic nude mice resulted in chronic infection and posterior paresis due to vertebral tumors and progressive multifocal leukoencephalopathy (PML), as seen with polyomaviruses in primates.  Vertebral tumors noted in beta2 microglobulin KO mice.

4.   Transmission: urine, contamination of environment (wild mouse nests)

5.   Duration: acute to chronic

6.   Comment: laboratory animal husbandry practices preclude the inefficient life cycle of this virus.  Polyoma virus is the type species of Polyomavirus Genus of Papoviridae.

 

Parvoviridae

    Minute Virus of Mice (MVM); Mice Minute Virus (MMV)

 

1.   Prevalence: common

2.   Diagnosis: serology (HAI, ELISA, IFA)

3.   Disease: Subclinical.  Experimental infection of neonates multisystemic, with cerebellar hypoplasia, renal infarcts, anemia, etc. Virus infection requires receptor. Replication (& cytolysis) requires S phase in dividing cells.  Natural disease with hematopoietic dyscrasia has been observed in immunodeficient mice (SCID, NOD, other KOs).  Experimental infection with MVMi results in disrupted hematopoiesis in C3H mice.

4.   Transmission: Contact. Vertical transmission shown experimentally

5.   Duration: variable; chronic, possibly latent. Experimental studies in immunocompetent mice suggest acute infection with recovery.

6.   Comment: 2 named strains, MVM-p (prototype) and MVM-i (immunosuppressive). Lymphoid tissues common target, with immunomodulation. New standards for nomenclature dictate that this virus now be called “mice minute virus (MMV). 

 

Parvoviridae

    Mouse Parvovirus (MPV); Mouse Parvovirus (MPV-1)

 

1.   Prevalence: common

2.   Diagnosis: serology (IFA, ELISA).  Recombinant non-structural antigen now used (NS-1) as antigen.  False positive reactions may rarely occur due to cross-reactivity with baculovirus components, resulting in low positive reaction to recombinant antigen, but negative to whole virus.

3.   Disease: Natural infections subclinical, but immunomodulation common (T cell tropic).

4.   Transmission: fecal?

5.   Duration: chronic, possibly latent.  MPV infects, and persists in, adult mice.

6.   Comment: Does not share virus structural antigens with MVM. HAI and MVM-based ELISA therefore inaccurate. Shares common non-structural antigens with other parvoviruses, including MVM. Thus IFA with MVM-infected cells as antigen works. Differs from rat parvovirus. Number of strains unknown.  Experimental infection induces allograft rejection. New nomenclature is MPV-1 (not to be confused with MMV-1).

 

Poxviridae

    Ectromelia Virus

 

1.   Prevalence: rare. Unknown natural origin.

2.   Diagnosis: serology, lesions.

3.   Disease: natural disease varies from subclinical to high mortality, depending upon mouse genotype, age, virus strain. Resistant adult mice recover early, with minimal virus shedding. Susceptible mice develop disseminated disease, with multifocal necrosis of liver, Iymphoid tissue, intestine, spleen, integument, etc. Fulminant infection may result in death with minimal virus excretion. Semi-susceptible mice develop disseminated infection with full manifestations, including rash and ectromelia (shortening of extremities due to dry gangrene). These mice serve as the major source of virus excretion. Pox inclusions (Cowdry A & B) in skin and mucosal epithelium.

4.   Transmission: skin, respiratory, urinary, fecal, etc.

5.   Duration: acute

6.  Comment: Genus Orthopox, Family Poxviridae. Several strains, including NIH-79, Wash-U, Moscow, Hampstead, St. Louis-69, Beijing-70, Ishibashi I-Ill, which vary in virulence. First description in England. Disease called mouse pox, virus called ectromelia virus…?????. Vaccine available (IHD-T), but modified live virus, prevents mortality but not infection with street virus, and causes seroconversion. Thus, not recommended except to protect valuable mice in imminent danger of exposure.  Beware of mouse serum that is commercially available. Latest incidence of laboratory mice developing mouse pox due to such serum occurred in 2003. 

 

Arenaviridae

    Lymphocytic Choriomeningitis Virus (LCMV)

 

1.   Prevalence: rare in laboratory mice, common in wild mice throughout the world, but focal distribution.

2.   Diagnosis: Serology, but mice tend to mount poor antibody responses, or antibody is complexed with antigen. Bioassay (intracerebral inoculation of infant vs. adult mice), MAP test or PCR.  Enzootically (in utero) infected mice are likely to be seronegative due to antibody complexed to high levels of antigen. Seroconversion of sentinels placed in the enzootically infected room is therefore needed for screening, but antibody titers are often low. PCR is useful in such situations.

3.   Disease: LCMV is non-cytolytic and does not directly cause disease. Disease associated with LCMV is immune-mediated, either through cytotoxic T lymphocytes (CTLs) or deposition of immune complexes. LCMV is maintained in naturally infected mouse populations through vertical transmission in utero from the dam to the early embryo. Pups infected in utero or in the first few hours of life have disseminated infections, including the thymus, so that T cells that traffic through the thymus become tolerant to the virus. Tolerance is LCMV specific, with normal immune response to other antigens and viruses. These mice are typically infected for life, and have CTL tolerance, but develop non-neutralizing antibody that is complexed with excess antigen.  As mice age, they develop “late disease” with immune complex arteritis and glomerulonephritis, as well as diffuse lymphocytic infiltrations in various tissues.  Mice infected as adults by natural routes recover from infection due to a vigorous CTL immune response, but with low or undetectable antibody.  Experimental inoculation of adult mice intracerebrally results in lymphocytic choriomeningitis. Mice die at around 5-6 days from seizures.  Disease is due to CTL-mediated pathology.  Inoculation of mice intraperitoneally or other routes results in CTL-mediated hepatitis, and lymphocytic infiltration of multiple tissues. Inoculation of mice with immunosuppressive strains of the virus results in early infection of dendritic cells (DCs), which express high levels of the viral receptor, alpha-dystroglycan. DCs in the marginal zones of the spleen and lymph nodes serve as a conduit of virus into the white pulp or T cell regions of the lymph nodes. CTLs attack DCs and T cells, resulting in severe lymphocytic depletion with global immunological exhaustion (not tolerance), and persistence of virus. In contrast, prenatally infected mice have selective tolerance to the virus. These mice also develop lymphocytic infiltrates in tissues and immune-complex arteritis and glomerulonephritis as they age.  Adoptive transfer of CTLs from immune mice to mice infected in utero leads to disease (lymphocytic choriomeningitis and hepatitis) and death, or recovery if they survive, whereas adoptive transfer of CTLs into mice infected as adults results in CTL exhaustion. Endocrinopathy also reported in mice infected prenatally or neonatally (growth hormone deficiency, thyroid deficiency, diabetes). Serositis is also a common lesion, regardless of route of inoculation.

4. Transmission: Early in utero transmission is important in the natural cycle of infection. Ova, placenta and early embryos are infected.  Virus transmitted via multiple routes, including mouse biological products.

5. Duration: acute to chronic, depending on age, tolerance, exhaustion, and immune status.

6. Comment: Mouse is natural reservoir host. Zoonotic agent. Hamsters pose a serious risk, as they develop persistent infections following natural exposure as adults (unlike mice).  Zoonotic infections have been reported in association with nude mice. Common laboratory strains of LCMV include Armstrong, Traub, WE, UBC, and Pasteur, and various substrains thereof. Virus strains are classified as “docile” or “aggressive” and “neurotropic’ or “viscerotropic” for experimental purposes. “Docile” and “viscerotropic” strains are actually more virulent, but cause no overt disease because they infect DCs and T cells, with severe immunodeficiency; whereas “aggressive” and “neurotropic” strains induce mild infections resulting in T cell-mediated disease. Intermediate scenarios also occur between the prenatal tolerant and the adult resistance forms of infection.  Natural infection of nude mice reported.

 

Arteriviridae

    Lactate Dehydrogenase-Elevating Virus (LDV)

 

1. Prevalence: rare in laboratory mice, common in wild mice

2. Diagnosis: persistent enzyme elevation in blood. Serology reported to be poor because of high avidity antigen-antibody complexes in serum.

3. Disease: Subclinical. Late onset demyelination in immunosuppressed C58 and AKR mice, but disease is associated with N-ecotropic retrovirus. Ecotropic retrovirus infects glial cells of these strains, making the neurons susceptible to LDV through still undetermined mechanism. Susceptibility of mouse strain to neurologic disease is linked to the fv-1n allele.

4. Transmission: Inefficiently transmitted among mice. Natural salivary transmission via bite wounds, and possible sexual transmission. 

5. Duration: persistent

6. Comment: select subpopulations of differentiated, but not precursor, macrophages and monocytes are the target of virus. Thus, persistent infection is maintained through continuous production of susceptible cells by the host.  LDV has a single neutralizing epitope that undergoes variation as a means of evading host immunity.  LDV can contaminate transplantable tumor lines, but virus can be eliminated by transient passage through rats. This virus is an arterivirus related to equine arteritis virus and simian hemorrhagic fever virus.  It belongs within the Order Nidovirales, which contains the Coronaviridae and Arteriviridae families.

 

Bunyaviridae (?)

    Hanta-like Virus

 

1. Prevalence: unknown

2. Diagnosis: no available diagnostic method

3. Disease: Subclinical.  Interstitial and perivascular nonsuppurative inflammatory lesions found in lungs of rats and mice.

4. Transmission: unknown

5. Duration: unknown

6. Comment: newly discovered agent in laboratory rodents. Most significant in rats, with pulmonary lesions, but experimental assays (PCR, serology.) suggest that laboratory mice are also naturally infected.  Much to be learned.  Probably not a Hanta virus.  People working with this agent seroconvert.

 

Caliciviridae

    Murine Norovirus-1 (MNV-1)

 

1.  Prevalence: according to RADIL, nearly 30% seroconversion among mouse samples tested

2.  Diagnosis:  serology

3.   Disease:  Not well characterized.  A single report of sporadic mortality among STAT1 and RAG2/STAT1 KO mice.  Intracerebral inoculation of virus resulted in encephalitis, vasculitis, meningitis, hepatitis, and pneumonia. “Postage stamp” pathology figures in the single report preclude evaluation of lesions. RAG1 and RAG2 KO mice inoculated i.c., p.o. or i.n. were not susceptible to mortality, but were persistently infected. IFN alpha/beta receptor, IFN gamma receptor, PKR or iNOS KO mice were not susceptible to mortality, but IFN apha/beta/gamma KOs were more susceptible to lethal infection. STAT1, STAT1/PKR and STAT1/RAG were all susceptible, indicating importance of STAT1 innate immunity.  Noroviruses in humans cause enteritis with villus blunting, nonsuppurative inflammation of lamina propria, but intestine not examined in mouse. 

4.    Transmission:  oro-fecal (presumptive, based upon other noroviruses). 

5.    Duration: unknown

6.    Comment:  Studies needed.  The mouse agent seems to “cluster” genetically differently from other noroviruses.  Cattle and pigs are also hosts to noroviruses, in addition to humans (Norwalk and other agents).

 

Coronaviridae

    Mouse Hepatitis Virus (MHV); Murine Hepatitis Virus

 

1. Prevalence: VERY common

2. Diagnosis: serology, lesions

3. Disease: epizootic - high mortality among neonates to subclinical among adults. Enzootic - usually subclinical in all ages, unless immunodeficient. Many virus strains, indistinguishable antigenically, but represented by 2 biotypes: respiratory and enteric. Respiratory strains replicate in nasal epithelium (minimal visible lesions in nose) and disseminate to varying degrees to secondary target organs, including lung, liver, lymphoid tissues, serosa, etc. in susceptible hosts. Focal necrosis with syncytia. Enteric strains largely restricted to bowel mucosa, with minimal dissemination. Ascending colon and cecum are major targets, with hallmark syncytia. Infant mice rapidly develop severe enteritis; adults infected and shed copious virus, but subclinical. Enteric disease is age-dependent, even in immunodeficient mice (related to mucosal kinetics, not immune response). Immunosuppression or co-infection with other agents increases susceptibility to MHV, but only during active infection.  Immunodeficient mice cannot clear infection.  Novel manifestations of infection are emerging in immunodeficient mice, such as granulomatous serositis (akin to feline infectious peritonitis?) in gamma interferon knock out mice.

4. Transmission: orofecal. In utero possible, but not likely.

5. Duration: acute in immunocompetent mice, but there are growing numbers of reports in which infection may be persistent in a variety of genetically altered mice.  B cell deficient mice may have mild or no clinical disease, but shed virus persistently. Regardless of immune status, genetic alteration, strain, etc. MHV infection is often subclinical but NOT LATENT!!!!

6. Comment: Coronaviruses of mice are antigenically related to rat coronaviruses, but biologically different. Immunity to MHV is virus strain-specific and short-lived. Coronaviruses are highly mutable, particularly in the S genes, which determine strain specificity. Thus, mice can be repeatedly infected, which has led to much confusion about the issue of latency. Coronaviruses readily mutate and recombine, with evolution of new strains and repeated infection features of enzootic infection.

 

 

 

 

Paramyxoviridae

    Pneumonia Virus of Mice (PVM); Murine Pneumonia Virus (MPV)

 

1. Prevalence: common

2. Diagnosis: serology; lesions in immunodeficient mice

3. Disease: subclinical upper respiratory infection in immunocompetent mice. Can cause lower respiratory disease in experimentally infected mice. Nude and SCID mice develop wasting disease due to progressive interstitial pneumonia (bronchiolar epithelium and type 2  pneumocytes).  Virus targets respiratory epithelial cells and type 2 pneumocytes.

4. Transmission: respiratory

5. Duration: acute (except immunodeficient mice)

6. Comment: Genus Pneumovirus; Family Paramyxoviridae. The International Union of Microbiological Societies 2000 has renamed PVM to MPV, which is confusing with mouse parvovirus (MPV-1)

 

Paramyxoviridae

    Sendai Virus; SeV

 

1. Prevalence: recently common, but now rare in US.  Still out there, though.

2. Diagnosis: serology, lesions

3. Disease: Sendai virus is the most clinically significant virus infection in laboratory mice because of its contagiousness and  likelihood to cause clinical disease in immunocompetent mice of all ages. Lesions are necrotizing rhinitis, tracheobronchitis, bronchiolitis and interstitial pneumonia. Target cells are respiratory epithelium and type 2 pneumocytes. Recovery phase characterized by hyperplasia and squamous metaplasia of respiratory epithelium, cuboidal metaplasia of alveoli, focal fibrosis. Virus is not cytolytic. Disease due to host immune attack on infected cells. Infection of athymic and SCID mice results in proliferative (rather than necrotizing) bronchiolitis and interstitial pneumonia. Marked variation in genetic susceptibility related to kinetics of immune response and/or mucociliary clearance, depending upon mouse strain. Predisposes to bacterial respiratory and ear infections.

4. Transmission: respiratory/aerosol

5. Duration: acute (except immunodeficient mice)

6. Comment: Genus Respirovirus; Family Paramyxoviridae.  Closely related to parainfluenza viruses.  Recent studies suggest that Sendai virus is likely to be zoonotic.

 

Picornaviridae

    Mouse Encephalomyelitis Virus (MEV); Theiler’s Murine Encephalomyelitis Virus (TMEV); mouse polio, GD VII

 

1. Prevalence: common

2. Diagnosis: serology, lesions (when present)

3. Disease: majority of infections are subclinical. CNS signs include convulsions, posterior paresis (flaccid) in a small fraction of mice. Infects enterocytes with minimal effect. CNS infection due to dissemination with acute encephalomyelitis (neuronolysis) and demyelination (primary and immune-mediated attack on infected oligodendroglia). Severity of CNS disease is virus strain-, host age- and genotype-dependent.

4. Transmission: orofecal

5. Duration: variable with intermittent shedding. Must be considered persistent.

6. Comment: Genus Cardiovirus; Family Picornaviridae.  Related antigenically to encephalomyocarditis (EMC) virus. Two serogroups: GD VII (GD VII, FA) and TO (TO, DA, BeAn 8386). TO group less virulent.  Inefficiently transmitted…test and cull at the cage level can eliminate from colony if use microisolator caging and proper changing technique. International Union of Microbiological Societies 2000 has renamed the entire virus group TMEV, although Theiler’s virus is only one strain!

 

Reoviridae

    Epizootic Diarrhea of Infant Mice (EDIM) Virus; Murine Rotavirus-A/EDIM (MuRV-A/EDIM)

 

1. Prevalence: common

2. Diagnosis: serology, lesions (if present), antigen in feces, E.M. of feces (many virions)

3. Disease: Lesions and diarrhea in mice infected at 12 or less days of age. All ages are susceptible to infection. Hydropic swelling of villus tip epithelium, malabsorption, diarrhea, runting.  EDIM is a disease of intestinal proliferative kinetics, with viral tropism for terminally differentiated enterocytes, which are in abundance in neonates. Diarrhea is not simply due to epithelial damage. Neuroendocrine effectors, viral enterotoxin secretagogue, and disruption of disaccharidases (with malabsorption) all factors, with E. coli overgrowth. Maternal immunity abrogates disease in enzootic infection.

4. Transmission: orofecal

5. Duration: acute, but not fully characterized

6. Comment: Genus Rotavirus; Family Reoviridae. Typical rotavirus (type A), antigenically related to type A rotaviruses of other species. Commercially available ELISA for fecal antigen is useful, but false-positive reactions can occur with some feeds. Disease related to mucosal epithelial kinetics, not immune status. Adult SCID mice, like immunocompetent mice, do not develop lesions.  International Union of Microbiological Societies 2000 has renamed MuRV-A/EDIM.

 

Reoviridae

    Reovirus 1,2,3; Murine Reovirus (MRV)

 

1. Prevalence: moderate

2. Diagnosis: serology

3. Disease: Usually subclinical. Historic literature describes CNS disease, hepatitis, diarrhea with steatorrhea and “oily hair effect (OHE).” Experimental inoculation of neonatal mice with prototype Reovirus 1 and 3 results in myocarditis, encephalitis and hepatitis, with virus replication in many tissues. Reovirus 2 causes EDIM-like lesions.

4. Transmission: orofecal

5. Duration: acute

6. Comment: Genus Orthoreovirus; Family Reoviridae. Mammalian reoviruses are divided into 3 serotypes: 1, 2 and 3, which represent many different strains. Reovirus 3 only serotype reported to cause natural disease in mice, but mice are susceptible to infection by all. Cross-react serologically, so cannot accurately distinguish infecting serotype.  International Union of Microbiological Societies 2000 has renamed the virus “Murine Reovirus (MRV)”, as if only mice are the only natural host and only mice are susceptible! 

 

Retroviridae

 

There are literally thousands of copies of retrovirus-like sequences scattered throughout the genome of the mouse.  These include IAP’s (intracisternal A particles), VL30’s (virus like 30S RNA sequences), MuRRS’s (murine retrovirus-related DNA sequences), GLN’s (tRNA glutathione like sequences), MuRVY’s (murine repeated virus sequences on the Y chromosome), and ETn’s (early transposons).  These are ancient acquisitions within the mouse genome, but remain active as retrotransposons, and contribute to spontaneous mutations and subline divergence.  More recent acquisitions that are included within the murine genome are endogenous MuLVs and MMTVs.  Exogenous MuLVs and MMTVs are horizontally transmissible, and not incorporated within the genome.

 

A.  Murine Leukemia Virus (MuLV)

 

1. Prevalence: 100%.  No laboratory or wild Mus musculus has been found without MuLV provirus within its genome.

2. Diagnosis: not done

3. Disease: variable, depending upon genotype of mouse. Disease manifestations may include neoplasia, demyelination, dilute color (DBA mice), hairlessness (HR mice), greyness, etc. Most MuLVs are not oncogenic.

4. Transmission: horizontal (exogenous) or vertical (endogenous). Endogenous proviruses inherited as Mendelian genetic characteristics  (up to 70 copies of ecotropic MuLVs are scattered throughout the genome in strain-specific patterns).

5. Duration: persistent, chronic and latent

6. Comment: Exogenous viruses are horizontally transmitted (through saliva, milk, semen) like conventional viruses, but no longer exist in laboratory mice. Wild mice have exogenous retroviruses and these are the historic source of some laboratory strains, including Friend, Moloney and Rauscher (FMR) viruses. Endogenous viruses are part of the mouse genome and all mouse strains carry endogenous provirus sequences, most of which are defective or incomplete. Each mouse strain has its own endogenous MuLV gene patterns, inserted in different multiple sites within the genome.  Because these proviruses are “genes,” they are given gene designations (for example, AKR mice carry multiple copies of the same endogenous provirus gene akv-1, akv-2, akv-3, akv-4).   Provirus sequences encode both replication competent (few) and replication-defective (many) viruses. These are major determinants of strain-specific characteristics. For example, MuLV germ line insertions result in dilute coat color of DBA mice and lack of hair in hairless mice.  Ecotropic (primarily endogenous viruses), xenotropic (primarily endogenous viruses), amphotropic (exogenous viruses in wild mice only), and polytropic (usually recombinants with different receptor tropism than amphotropic) behavior and host determinants (restriction genes fv-1, -4) and receptors are important in evolution of recombinant viruses which are pathogenic.   Non-replicating, endogenous MuLV sequences can recombine with replication-competent MuLVs to produce oncogenic recombinants, called mink cell focus (MCF) forming viruses that are capable of circumventing host receptor restriction (interference) as polytropic viruses with alternate receptors. Important host determinant is fv-1, with B (BALB) and N (NIH) alleles that determine specificity of Friend virus (Fv), and other ecotropic MuLVs. Expression of non-oncogenic endogenous MuLVs occurs at different times and in different tissues, with evolution of recombinant, oncogenic variants (sometimes). MuLVs are often called “acute” or “non-acute,” referring to rate of cancer induction.  Acute viruses are largely experimental anomalies that have transposed host proto-oncogenes that have direct and immediate effects upon host cell division and are “defective.”  Defective viruses need “non-acute” ecotropic virus to complete replication (“helper” virus).  Acute viruses are often associated with sarcomas…thus once called “sarcoma” viruses.  Non-acute MuLVs occur naturally, and are represented by the endogenous, replication-competent forms.  These viruses have longer latent periods for induction of disease, and generally work by genomic insertion (in contrast to proto-oncogene effects of acute viruses).

 

B.  Murine Mammary Tumor Virus (MMTV)

 

I. Prevalence: nearly 100% among laboratory strains of mice, although there is a line of “Lake Casitas” mice that was found without endogenous mtv. 

2. Diagnosis: not done

3. Disease: variable expression of mammary neoplasia and lymphoproliferative disease, depending upon mouse strain.

4. Transmission: same as MuLV. Exogenous (Bittner milk agent or MMTV-S) transmitted via milk, saliva & semen. Endogenous provirus (0 to 4 copies) in genome of most strains, with gene designations…mtv-1, mtv-3, etc.  Previously named MMTV-O, -P, -L, -X, etc.

5. Duration: persistent

6. Comment: Exogenous viruses eliminated by foster nursing or rederivation. Bittner agent intentionally maintained in some populations of C3H mice as a model system (C3H-MMTV+).  SJL mice develop B cell lymphoproliferative disease due to expression of MMTV T cell superantigen (Sag).  B cells express Sag, which acts as a T cell mitogen which stimulates T cells to elaborate lymphokines in excess, resulting in B cell proliferation.  B cells that express virus home to mammary gland, allowing infection of mammary tissue and subsequent virus excretion in milk.  Ecotropic MMTV is also responsible for thymic leukemia in GR mice. Thus, not all MMTVs produce mammary tumors, and some produce leukemias.   Unlike MuLVs, MMTVs do not depend upon recombination for oncogenesis, but rather direct insertional activation of proto-oncogenes.  The LTR region of MMTV is used as a mammary gland specific promoter in transgene constructs. Although other species, including humans, have mammary tumor virus sequences within their genome, the mouse is the only species that is known to have replication-competent mammary tumor virus.

 

 

*  International Union of Microbiological Societies (2000). Virus Taxonomy. Seventh Report of the International Committee on Taxonomy of Viruses.  MHV van Regenmortel, et al. (Eds), Academic Press, San Diego, pp. 311-323.


II. BACTERIA

 

Burkholderia gladioli

Chlamydia muridarum

Chlamydophila psittaci

Cilia-Associated Respiratory (CAR) Bacillus

Citrobacter rodentium

Clostridium difficile

Clostridium perfringens

Clostridium piliforme (aka Bacillus piliformis)

Corynebacterium bovis

Corynebacterium hoffmani

Corynebacterium kutscheri

Eperythrozoon coccoides

Escherichia coli

Helicobacter spp.

Klebsiella oxytoca

Lawsonia intracellularis

Leptospira ballum

            Mycobacterium avium-intracellulare

            Mycobacterium chelonae

            Mycoplasma spp.

Pasteurella pneumotropica

Proteus mirabilis

Pseudomonas aeruginosa

Salmonella enterica

Staphylococcus aureus

Staphylococcus xylosus

Streptobaeillus moniliformis

Streptococcus spp.

 

Burkholderia gladioli

 

1.  Prevalence: uncommon

2.       Diagnosis: lesions, culture

3.   Disease:  otitis media in athymic nude mice

4.       Transmission: orofecal (presumptive)

5.       Duration:  unknown

6.       Comment: Single case report of outbreak among nude mice.  Bacterium isolated from environment, feces, sipper tubes, drinking water, and soiled bedding.  Consistently isolated from oropharynx. 

 

Chlamydia muridarum

 

1. Prevalence: unknown, but probably rare

2. Diagnosis: lesions, isolation (cell culture, egg inoculation, elementary bodies in impression smears, serology-IFA)

3. Disease: no natural disease reported, except after serial mouse-mouse passage of lung tissue from subclinically infected mice. Eventually causes interstitial pneumonia, with dyspnea.

4. Transmission: probably respiratory.

5. Duration: probably persistent.

6. Comment: “Nigg” agent. Clara Nigg discovered it during attempts to isolate influenza virus from human throat washings by intranasal inoculation of mice. Also called “grey lung disease” agent and mouse pneumonitis agent. Mouse biovar (MoPn) was once thought to be C. trachomatis, but it does not share type-specific antigens with 2 human strains of C. trachomatis (bivars trachoma and lymphogranuloma venereum).  Recent evaluation of 16S rRNA sequences have reclassified the Chlamyidae into two major phylogenetic groups: Chlamydophila, which branches into three clusters, including C. pneumoniae, C. pecorum, and a third group which includes C. psittaci, C. abortus, C. caviae, and C. felis; and Chlamydia, which branches into two major groups of C. suis and a branch including C. trachomatis and C. muridarum.  Thus, C. muridarum is now considered closely related to C. trachomatis, but genetically distinct. MoPn is increasing in popularity as an experimental respiratory infection model.

 

Chlamydophila psittaci

 

1. Prevalence: sporadic

2. Diagnosis: elementary bodies in impression smears, egg isolation.

3. Disease: pulmonary lesions in mice following serial intranasal passage of lung tissue; splenomegaly, hepatomegaly, serofibrinous peritonitis with ascites in mice following i.p. passage of liver/spleen tissue. Natural infection apparently subclinical and persistent.

4. Transmission: probably respiratory.

5. Duration: probably persistent.

6. Comment: little is known about natural C. psittaci infection in mice, but it has been documented at least twice in the 1970’s in conventional mice following mouse-mouse passage of mouse tissue.  See Comments under Chlamydia, above.

 

Cilia-Associated Respiratory (CAR) Bacillus

 

1. Prevalence: common

2. Diagnosis: serology available, but not used much in US.  PCR increasing. Although apparent on H&E to the trained observer, silver stains reveal organisms among cilia of respiratory epithelium. 

3. Disease: None to chronic suppurative pneumonia.  Experimental infection results in peribronchiolar lymphoplasmacytic infiltrates, similar to Mycoplasma.  Probably also a B cell mitogen.  Experimental studies reveal lesions to be more severe in BALB mice vs. B6 mice. Mice are more susceptible to experimental infection than rats, but natural disease is more prevalent in rats. Can be a co-­infection with Mycoplasma pulmonis, Sendai virus, etc.

4. Transmission: direct contact

5. Duration: chronic

6. Comment: Rats, rabbits, humans also infected with CAR bacilli, but with antigenically diverse members of the group.  CAR Bacillus is an unclassified agent related to Flexibacter and Flavobacterium spp. (gliding bacteria group).

 

Citrobacter rodentium (Transmissible Murine Colonic Hyperplasia)

 

1. Prevalence: rare

2. Diagnosis: culture, lesions. Must culture multiple mice in early stage of infection, as agent is often absent when clinical signs and lesions are overt.

3. Disease: rectal prolapse, sticky feces. Thickening of the descending colon and cecum due to mucosal hyperplasia. Inflammation and erosion variable, but tend to occur most in young mice. Genotype, age and diet are factors. Agent attaches to surface mucosa, but disappears at the time of peak disease (around 2 weeks).  Immunodeficient mice cannot eliminate organisms, but develop mild, transient lesions.  Thus, acquired immune responses appear to play a role in pathogenesis.

4. Transmission: direct contact, inefficient

5. Duration: acute (around 2 weeks) with no carrier state

6. Comment: Old name was Citrobacter freundii; pathogenic strain (4280).  Agent is non-motile with characteristic sugar fermentation profile. Not all Citrobacters are pathogenic in mice and C. rodentium does not cause disease in other species. Eliminate by improving husbandry.  This agent is currently popular as a model bacterium for studying attaching and effacing enteropathogenic E. coli (EPEC) and enterhemorrhagic E. coli (EHEC).  C. rodentium, EPEC and EHEC share a similar pathogenicity island called locus of enterocyte attachment (LEE) that carries the determinants for type III secretion system.  Type III secretion system allows the bacteria to secrete proteins into target cells, which then facilitate attachment. 

 

Clostridium difficile

 

1.  Prevalence: unknown, but common in some sources of mice

3.       Diagnosis: lesions, culture, toxin assay.

3.   Disease:  thrombosis and necrosis of duodenal villus tips, mucosal edema, enterocyte necrosis and exfoliation with mild hyperplasia in large intestine.

7.       Transmission: orofecal

8.       Duration:  unknown, but possibly transient as with other Clostridia.

6.   Comment: Clostridial overgrowth with enteropathy is symptomatic of another underlying factor, such as antibiotic “toxicity”, dysbiosis, stress, diet change, etc. Mice can develop enteric lesions with overgrowth of C. perfringens, C. difficile, and possibly C. spiroforme.

 

Clostridium perfringens

 

1. Prevalence: rare

2. Diagnosis: culture, toxin assay, lesions

3. Disease: sporadic outbreaks of necrotizing enterocolitis in post-weaning mice and lactating mice. Lesions consist of mucosal necrosis, hyperplasia and edema.

4. Transmission: orofecal

5. Duration: unknown

6. Comment:  Clostridial overgrowth with enteropathy is symptomatic of another underlying factor, such as antibiotic “toxicity”, dysbiosis, stress, diet change, etc. Mice can develop enteric lesions with overgrowth of C. perfringens, C. difficile, and possibly C. spiroforme.

 

Clostridium piliforme (Tyzzer’s Disease)

 

1. Prevalence: rare (once common)

2. Diagnosis: PCR of feces or tissues. Lesions are diagnostic, with the use of special stains to reveal typical intracytoplasmic organisms.  Serology developed but often not used in US.

3. Disease: Sudden death with or without diarrhea. Colitis and/or typhlitis with dissemination to liver (focal hepatitis) and occasionally heart (myocarditis). Special stains (silver, Giemsa, PAS) reveal intracytoplasmic fascicles of bacteria. Enteric lesions have intracellular fascicles of organisms in enterocytes, and smooth muscle necrosis (with fewer organisms) is frequent.  Immunosuppression exacerbates disease in carrier mice and stress predisposes to disease. Resistance to disease has been reported to be B-cell mediated. In experimental studies, nude mice (T cell deficient) were no more susceptible to disease than immunocompetent mice, but in other studies, the converse seemed to be true. 

4. Transmission: Orofecal via spores. Spores survive for > 1 year.  Recent experience suggests that transmission appears to be mediated by direct contact and the agent may not be highly contagious. 

5. Duration: unknown

6. Comment: Old name was Bacillus piliformis.   Cannot be grown in cell-free medium, but can be grown in cell culture. Partial species-specificity of isolates. Depopulate.  In a recent outbreak, T cell receptor beta knock out mice had clinical disease, but other triggering events seem to be needed, even in SCID, RAG and NUDE mice.  Probable triggering mechanism is weaning, intestinal dysbiosis, and other stressors.

 

Corynebacterium bovis (pseudodiphtheriticum)

 

1. Prevalence: rare

2. Diagnosis: culture, lesions, Gram stain of lesions.

3. Disease: orthokeratotic dermatitis in nude mice. High mortality in suckling mice, transient disease in weanlings, asymptomatic in adults.

4. Transmission: contact

5. Duration: unknown

6. Comment: sporadic problem in nude mouse colonies

 

Corynebacterium hoffmani

 

1. Prevalence: common

2. Diagnosis: culture, lesions

3. Disease: conjunctivitis, especially in BALB mice

4. Transmission: direct contact

5. Duration: unknown, chronic

6. Comment: frequently associated with conjunctivitis, but cause-and-effect not fully established. Probably opportunistic pathogen.

 

Corynebacterium kutscheri (Pseudotuberculosis)

 

1. Prevalence: rare (once common)

2. Diagnosis: culture, Gram stain of lesions, serology (not used)

3. Disease: Caseopurulent abscesses containing prominent colonies of Gram-positive bacilli (Chinese letter configurations) at edge of lesions. Lesions in liver, kidney, lung and other sites. Cervical lymph nodes may be enlarged, but not abscessed. Subclinical carrier state common. Immunosuppression and other stressors cause exacerbation of disease.

4. Transmission: direct contact

5. Duration: chronic, but probably not latent

6. Comment: Pathogenesis not fully understood in mouse (see rat). Depopulate.

 

Eperythrozoon coccoides

 

1. Prevalence: rare (once common)

2. Diagnosis: blood smear, Giemsa stain; splenectomy/immunosuppression

3. Disease: subclinical or anemia, splenomegaly, RE proliferation. Intra- and extracellular forms

4. Transmission: via blood; Polyplax serrata vector

5. Duration: chronic, with eventual recovery

6. Comment: potentiates MHV, LCMV, LDHV. Occasional contaminant of biological products.  No longer considered Rickettsiales; reclassified as a member of Class Mollicutes, Order Mycoplasmatales (related to Mycoplasma).

 

Escherichia coli

 

1. Prevalence: common intestinal inhabitant, disease variable

2. Diagnosis: culture, lesions

3. Disease: hyperplastic typhlocolitis in immunodeficient mice (SCID and multiple deficient, but not nude). Overgrowth in infant mice with viral enteritis.

4. Transmission: orofecal

5. Duration: chronic

6. Comment: Immunodeficient mice infected with an otherwise non-pathogenic, non­lactose fermenting E. coli.  Some of these infections may be mis-diagnosed Citrobacter rodentium, but others seem to be E. coli (author’s experience). Disease requires multiple immune deficiencies, and may be complicated by Helicobacter.  Reports of this agent/disease were before awareness of Helicobacter, which produces similar lesions.  Other typical E. coli strains may overgrow in infant mice with viral enteritis.

 

Helicobacter hepaticus

H. bilis

H. muridarum

H. rodentium

H. typhlonius

H. ganmani

et al.

 

1. Prevalence: presumably common, but unknown

2. Diagnosis: lesions, silver stain, culture (requires special medium, microaerophilic conditions); PCR; membrane antigen extract ELISA (has partial species specificity). Recombinant protein antigens tend to be sensitive and specific, but not useful for detecting cross-reactive antibody against all species of Helicobacter. 

3. Disease: acute to chronic hepatitis, which may be associated with increased incidence of hepatic neoplasia; chronic typhlocolitis, proliferative typhlocolitis

4. Transmission: oro-fecal

5. Duration: chronic

6. Comment: There are 27 named species of Helicobacter, and over 35 yet to be named. They infect a wide variety of host species, and appear to have only weak host species specificity.  Mice can be naturally infected with H. hepaticus, H. bilis, H. muridarum, H. (Flexispira) rappini, H. rodentium, H. typhlonius, H. ganmani and probably other unnamed species.  Mice can be experimentally infected with an even longer list, including H. trognontum (isolated from rats). H. muridarum may be associated with chronic gastritis. H. hepatiticus and H. bilis, separately or in combination and possibly other species, are associated with chronic typhlocolitis in immunodeficient mice. Infection with one may modify disease caused by another, such as the protective effect of H. hepaticus that has been demonstrated in mice experimentally infected with H. bilis.  Infection of mice with Helicobacter has been shown to abrogate sensitivity to experimental allergic encephalomyelitis in some strains of mice. As awareness of these syndromes increases, typhlocolitis has been found in immunosufficient mice that are naturally infected with H. hepaticus, including A/J, BALB/c, Swiss Webster and ICR mice. There is a curious gender pattern of disease susceptibility to H. hepaticus, with male mice being more susceptible to hepatitis, and females to enterocolitis. There is also a mouse genotype-related susceptibility to H. hepaticus disease, with A/JCr mice noted to be susceptible and C57BL mice resistant, and this is reflected in antibody titers.  Flexispira rappini is Helicobacter, based upon 16S ribosomal DNA gene sequence, but sequence data also reveal that H. rappini is a mixture of Helicobacter species.  Helicobacter-infected mice may be bacteremic, as evidenced by contamination of transplantable xenografts in SCID mice.

 

Klebsiella oxytoca

 

1. Prevalence: low

2. Diagnosis: culture

3. Disease: unusually high prevalence of suppurative female reproductive tract lesions reported in an infected colony of aging mice.  Also associated with ascending urinary tract infections and otitis media.

4. Transmission: contact

5. Duration: chronic

6. Comment: this bacterium is basically an opportunistic bacterium, similar to other gram-negative bacteria in the mouse. 

 

Lawsonia intracellularis

 

1. Prevalence: low

2. Diagnosis:  lesions, PCR, and silver stains reveal typical coccobacillary forms in apical cytoplasm of enterocytes.

3. Disease: proliferative bowel lesions.

4. Transmission: orofecal (presumptive)

5. Duration: chronic (presumptive)

6. Comment: Lawsonia intracellularis is a single species of bacterium with no known genetic, biologic, or serologic differences detectable among isolates derived from birds and a wide variety of animals.  Thus, this pathogen has a wide host range, and since it commonly infects laboratory hamsters, rats, rabbits, and other species, the opportunity for mouse exposure is there.  Mouse infection is not reported in literature, but it has been observed and verified by PCR.

 

Leptospira ballum

 

1. Prevalence: rare in laboratory mice, common in wild mice. Not tested for in laboratory mice, so true prevalence not known.

2. Diagnosis: culture

3. Disease: none in mice.

4. Transmission: urine

5. Duration: chronic

6. Comment: L. ballum is the most common leptospire in wild mice and mouse-associated zoonoses. Mice do not generally develop lesions.

 

Mycobacterium avium-intracellulare

 

1. Prevalence: rare

2. Diagnosis: lesions, Acid-fast stains, culture

3. Disease: granulomata in lungs, liver, mesenteric lymph nodes reported in C57BL/6 mice.

4. Transmission: water?

5. Duration: chronic

6. Comment: single report. C3H/HeN and B6C3FI mice, F344 rats negative.

 

Mycobacterium chelonae

 

1.  Prevalence: rare

2.   Diagnosis: lesions, Acid-fast stains, culture

3.   Disease: granulomatous inflammation of the tail in immunodeficient mice

4.   Transmission: contact?

5.   Duration: chronic

6.   Comment: single report

 

 

Mycoplasma pulmonis

M. arthritidis

M. neurolyticum

M. collis

 

1. Prevalence: M. pulmonis moderate. M. arthritidis less common and others rare or nonexistent.

2. Diagnosis: culture, serology, lesions (if present), Serology utilizes M. pulmonis as antigen, with variable cross-reactivity among different strains. M. arthritidis infection can cause seroconversion to M. pulmonis.

3. Disease: Mycoplasmosis.  M. pulmonis is associated with chronic respiratory disease. It tends to produce chronic suppurative rhinitis, otitis and bronchopneumonia in mice, often in concert with other agents (Sendai virus, CAR bacillus, etc.). Mycoplasmas attach to apical cell membranes of mucosal epithelial cells. M. pulmonis, M. arthritidis and M. neurolyticum inhabit the upper respiratory tract and M. collis inhabits the genital tract. Only M. pulmonis is a significant natural pathogen. Infections are often subclinical, but disease can be precipitated by viral infections. M. arthritidis and M. pulmonis cause arthritis when given intravenously and M. neurolyticum elicits an exotoxin causing neurolytic “rolling disease” when given intracerebrally.  B6 mice are disease-resistant.

4. Transmission: respiratory, other

5. Duration: chronic

6. Comment: depopulate. Test and cull can be effective.  Mycoplasma is a strong B cell mitogen, resulting in typical lymphoplasmacytic infiltrates in peribronchiolar regions of infected rodents.  Recently, M. arginni, a contaminant of a human cell line, was found to be associated with polyarthritis in SCID mice inoculated with contaminated cultured human cells. 

 

Pasteurella pneumotropica

 

1. Prevalence: high prevalence of infection, sporadic disease

2. Diagnosis: culture, lesions

3. Disease: opportunistic organism. Normal gut microflora. High frequency of isolation from nasopharynx and gut of normal mice. Associated with conjunctivitis, ophthalmitis, periorbital abscesses, otitis, pneumonia, cystitis, prepucial gland abscesses, subcutaneous abscesses, pyometra, etc. Dermatitis in nude mice.

4. Transmission: normal flora

5. Duration: chronic

6.  Comment:  emerging disease is suppurative bronchopneumonia in partially immunodeficient mice co-infected with Pneumocystis murina.  Opportunistic pathogen.

 

Proteus mirabilis

 

1. Prevalence: agent common, disease sporadic

2. Diagnosis: culture, lesions

3. Disease: genitourinary infections, otitis. Septicemia reported in immunodeficient mice:  fibrinopurulent peritonitis, hepatitis, pneumonitis, splenomegaly and significant mortality noted in SCID mice.

4. Transmission: contact, environmental

5. Duration: unknown

 

Pseudomonas aeruginosa

 

1. Prevalence: agent common, disease conditional

2. Diagnosis: culture, clinical disease associated with neutropenia

3. Disease: Opportunistic. Mice that are exposed to organism while neutropenic (x-irradiation, cytoxan) develop bacteremia and high mortality. Pseudomonas does not permanently colonize mice, but passes transiently through GI tract following exposure from water bottle sipper tubes. Organisms invade naso-squamous junction in nose.

4. Transmission: water bottle (sipper tube) contamination

5. Duration: transient but repeated infection

6. Comment: control with water treatment (acidification or chlorination).  Water treatment has become an industry standard, but may cause more morbidity (dental erosion) than Pseudomonas.

 

 

 

Salmonella enterica

 

1. Prevalence: rare (once common)

2. Diagnosis: culture, lesions. Mesenteric lymph nodes are most consistent site for culture.

3. Disease: Salmonellosis.  Normal microflora contribute resistance. Bacteria invade Peyer’s patches of ileum to mesenteric lymph nodes to liver, spleen and blood, bile ducts, intestine (enterohepatic cycle). Disease dependent upon host/agent factors. Lesions include enteritis (terminal small intestine and cecum), mesenteric lymphadenopathy, Peyer’s patch hyperplasia, hepatic granulomas, splenomegaly. Infection is often subclinical.

4. Transmission: intermittent fecal shedding

5. Duration: usually less than 1 month. Approximately 5% carrier rate among mice in an infected population.

6. Comment: Salmonella classification continues to change. Mammalian Salmonellas are now grouped under S. enterica, with over 2500 named serovars All serovars are potentially pathogenic, but serovar typhimurium is most common in naturally infected mice. Zoonotic agent. Depopulate.

 

Staphylococcus aureus

 

1. Prevalence: common

2. Diagnosis: culture, lesions

3. Disease: Abscesses, especially cervical lymph nodes with botryomycotic features in immunocompetent mice. Furunculosis and cervical lymph node abscesses in nude mice. Ulcerative dermatitis, often secondary to hypersensitivity dermatitis due to acariasis.  Lesions feature prominent colonies of bacteria in surface exudate, with coagulation necrosis to varying depths of the skin. Skin lesions are reminiscent of burns associated with production epidermolytic exotoxins (analogous to Staphylococcal Scalded Skin Syndrome in humans). Epidermolysins are plasmid-encoded, with evidence of transfer to Streptococcus mutans. Also a factor in Staphylococcus hyicus dermatitis in pigs. 

4. Transmission: environmental

5. Duration: chronic

 

Staphylococcus xylosus

 

1. Prevalence: common

2. Diagnosis: culture, lesions

3. Disease: Lesions on the tail of SJL mice reported, with most severely affected having sloughing and necrosis of tail. Also report of ulcerative dermatitis in nude mice. Microscopic features similar to Staphylococcus aureus burn-like lesions.

4. Transmission: environmental

5. Duration: chronic

 

Streptobacillus moniliformis

 

1. Prevalence: rare in laboratory mice

2. Diagnosis: culture - pleomorphic, non-motile filamentous rods

3. Disease: septicemia, diarrhea, conjunctivitis, hepatitis, serosal hemorrhages, and suppurative arthritis.

4. Transmission: carried and introduced by rats, then mouse-to-mouse contact transmission

5. Duration: chronic

6. Comment: carried in oropharynx of rats. Cause of rat-bite fever in humans (also Spirillum minus)

 

Streptococcus spp.

 

1. Prevalence: low

2. Diagnosis: culture, lesions

3. Disease: outbreaks of high incidence ulcerative dermatitis reported with beta hemolytic Streptococcus. Alpha hemolytic Streptococcus also reported in SCID mouse septicemia, Group B Streptococcus reported to cause rhinitis, meningitis and encephalomyelitis in nude mice.  Endocarditis sporadic.  Recent reports of dermatitis associated with Streptococcus zooepidemicus.

4. Transmission: contact

5. Duration: chronic

6. Comment: mice resistant to Streptococcus pneumoniae (Diplococcus)

 

 

7.       FUNGI

        

       Aspergillus sp.

       Encephalitozoon cuniculi

       Paecilomyces variotii          

       Trichophyton mentagrophytes

       Pneumocystis murina

 

 

 

Aspergillus sp.

 

1. Prevalence: rare disease

2. Diagnosis: lesions, culture

3. Disease:  pulmonary granulomas due to Aspergillus terreus in immunodeficient genetically altered mice (gp91 phox null) maintained on corncob bedding.

4. Transmission: inhalation from contaminated corncob bedding

5. Duration: chronic

6. Comment: opportunistic fungus: see Paecilomyces, below.

 

Encephalitozoon cuniculi (formerly Nosema muris, E. muris, E. rabii, N. cuniculi)

 

1.  Prevalence: rare

2.  Diagnosis:  lesions (rare), serology (not usually done), Gram stain for spores

3.  Disease:  Clinical signs in immunocompetent mice are negligible. Ascites and retardation of transplantable tumor growth have been reported.  Immunodeficient mice (cortisone-treated, nudes, etc.) develop lethal disease, with ascites, wasting syndrome, enteritis, encephalitis, hepatitis, interstitial nephritis, splenomegaly.  Microscopic findings include necrosis and nonsuppurative inflammation of multiple tissues, with numerous organisms.

4.  Transmission:  urine, transplantable tumors.

5.  Duration:  persistent

9.    Comment:  E. cuniculi is a common microsporidian parasite that infects a wide variety of mammals, including rabbits, guinea pigs, rats, mice, horses, foxes, cats, dogs, muskrats, leopards, baboons, and humans.  There are three major genotypes, among which rabbit agent is genotype I, most human isolates are genotype III, and mouse isolates appear to be genotype II.  Host species specificity may not be strict, as there are also group I human isolates. Mice are natural host for E. cuniculi only.  Most isolates from other species are generally not available for genotyping, or have not been genotyped. Spore infects target cell through extrusion of polar tube, with injection of sporoplasm, which proliferates into many plasmodial cells (aka meronts) within parasitophorus vacuole.  Develop into sporonts which undergo binary fission to sporoblasts, then spores, which are infectious for adjacent cells.  Spores shed into environment via urine. Now considered to be a member of Kingdom Fungi. 

 

Paecilomyces variotii

 

1. Prevalence: rare disease, commonly isolated from respiratory tract of rodents

2. Diagnosis: lesions, culture

3. Disease: infection usually subclinical. Pulmonary abscesses in NADPH oxidase deficient gp91phox null mice.  Note similarity to Aspergillus (above)…opportunistic.

4. Transmission: contact.

5. Duration: chronic

6. Comment: opportunistic fungus with similar opportunistic behavior in immunodeficient humans.

 

Pneumocystis murina sp. nov.

            Formerly P. carinii f. sp. muris

 

1. Prevalence: high rate of infection; disease rate low, except in immunodeficient mice (common)

2. Diagnosis: silver stain of lung lesions for cysts

3. Disease: not pathogenic for immunocompetent host. Steroids/low protein diet and immunodeficient genotypes allow overgrowth. Lungs firm, pale, mottled and do not collapse. Alveoli contain eosinophilic proteinaeceous exudate containing numerous trophic forms and cysts visible with silver stain. Trophic forms attach to type II pneumocytes.  Interstitial pneumonia to varying degrees, depending upon host.

4. Transmission: contact aerosol.  Immunocompetent mice can serve as carriers and transmit infection.

5. Duration: chronic, mediated by major surface glycoprotein (MSG) antigenic variation.

6. Comment: Rederive or replace immunodeficient mice. Serious life-limiting disease in nude, SCID and other immunologically deficient mice. Disease features vary with immune defect and exacerbated by virus infection, particularly PVM.  Marginally immunodeficient, genetically modified mice may manifest atypical, mild forms of Pneumocystis pneumonia. Mouse, rat, human Pneumocystis differ genetically, based upon 18S rRNA gene sequence.  Human agent is now P. jirovecii, rat agents are P. carinii and P. wakefieldiae

 

Trichophyton mentagrophytes

 

1. Prevalence: rare disease

2. Diagnosis: lesions, culture, histochemistry

3. Disease: infection usually subclinical. Alopecia, focal crusts, especially on head. Favus in severe cases (yellow crusts on muzzle, head, ears, tail, extremities). Hair invasion is not a feature of mouse dermatomycosis.

4. Transmission: contact. Non-selective host range, including humans

5. Duration: unknown

6. Comment: nearly non-pathogenic in mouse. Disease/lesions exceedingly rare

 

 

 

IV. PROTOZOA

 

Cryptosporidium muris, parvum

Eimeria spp.

Giardia muris

Klossiella muris

Sarcocystis muris

Spironucleus muris

 

Cryptosporidium muris,

C. parvum

 

1. Prevalence: rare

2. Diagnosis: histology, cysts in feces

3. Disease: both agents are mildly pathogenic and opportunistic, associated with enteritides of various primary origin, malnutrition, and immunodeficiency. Runting in infant mice. Sticky feces and weight loss in immunodeficient mice. Attach to brush border of surface epithelium of stomach (C. muris) or small intestine (C. parvum). Cholangitis with focal hepatic necrosis observed in nude mice infected with C. parvum.  Lymphoplasmacytic infiltration of lamina propria, mild mucosal hyperplasia.

4. Transmission: orofecal, oocysts

5. Duration: unknown

6. Comment: opportunistic overgrowth. Treat primary problem.  BOTH C. muris and C. parvum are zoonotic. Sporozoites invade epithelium, develop within parasitophorus vacuole into type I merozoites, which replicate asexually with rupture of host cell, reinvasion of other epithelial cells with development into type I or type II merozoites.  Type II merozoites develop into micro- and macrogametes, which form oocysts.  Apical complex provides intimate association with host cell.  Unique intracellular, extracytoplasmic location. 

 

 

Eimeria spp.

 

1. Prevalence: rare (common in wild mice)

2. Diagnosis: oocysts in feces, lesions

3. Disease: enteritis, typhlitis, colitis with diarrhea, blood. Especially found in young (weanling) mice. E. falciformis in cecum and colon; E. vermiformis in distal small intestine; E. papillata in distal small intestine; E. ferrisi in cecum and colon. 

4. Transmission: orofecal (oocysts)

5. Duration: moderate chronicity with recovery and strong immunity

6. Comment: Eighteen species of Eimeria have been described in Mus musculus, of which 4 species  are pathogenic (E. falciformis, E. vermiformis, E. papillata, and E. ferrisi).  Meronts, microgametes, macrogametes and oocysts. 

 

Giardia muris

 

1. Prevalence: low (common in wild mice)

2. Diagnosis: cysts in feces; trophozoites in small intestine (wet mounts or histology)

3. Disease: often subclinical. Abdominal distention, yellow-white watery digesta in small intestine. Trophozoites aligned along brush border of villi. Lymphoplasmacytic infiltrates of duodenal and jejunal lamina propria. Opportunistic pathogen in mice, usually associated with other primary disease or immunodeficiency. Nude mice develop chronic enteritis, weight loss.

4.   Transmission: orofecal (cysts)

5.   Duration: approximately 1 month, except in immunodeficient mice

6.   Comment: treatment controls disease. Hamsters frequently infected and infections

are chronic with chronic malabsorption, enteritis, diarrhea, weight loss.

 

Klossiella muris

 

1.   Prevalence: rare, except in wild mice (very common)

2.   Diagnosis: histology, oocysts in urine

3.  Disease: usually subclinical. Key target is kidney. Sporozoites enter portal bloodstream after ingestion of sporocysts, spread throughout the body. Schizogony in glomerular endothelium (usually not apparent); gametogeny and sporogony in tubular epithelium is obvious feature, with nonsuppurative interstitial nephritis.

4.   Transmission: urine (sporocysts)

5.   Duration: chronic.

6.     Comment: depopulate or rederive

 

Sarcocystis muris

 

1.   Prevalence: rare, except in wild mice.  Reports in laboratory mice seem to be on the rise.

2.   Diagnosis: histology, cysts in skeletal and heart muscle.

3. Disease: Sarcocysts filled with bradyzoites in myofibers of skeletal muscle and heart (less common). Incidental finding.

4.  Transmission: feed contaminated with cat feces, or cannibalism of other infected mice. Cockroaches exposed to cat feces can transmit to mice.

5.   Duration: chronic.

6.  Comment: depopulate, rederive and/or break infectious cycle.  Cat is definitive host.

 

Spironucleus muris (formerly Hexamita muris)

 

1.   Prevalence: common

2.   Diagnosis: cysts in feces (Easter eggs); trophozoites in small intestine (wet mounts, histology)

3.  Disease: usually subclinical. Opportunistic overgrowth with immunosuppression, immunodeficiency, enteritides of various origin, especially enterotropic MHV. Watery fluid and gas in upper small intestine. Trophozoites seek refugfe in crypts and may distend them. Mucosa hyperplastic and trophozoites may invade lamina propria. Nude mice develop chronic hyperplastic enteritis.  Trophozoites in crypt lumina of distal small intestine.  Occasional invasion of lamina propria.

4.   Transmission: orofecal (cysts)

5.   Duration: chronic

6.  Comment: treatment controls disease. Eliminate primary pathogen. The syndrome of spironucleosis is rare and if present, other pathogens (especially enterotropic MHV) should be sought.  Spironucleosis can also be seen in immunodeficient mice without other pathogens. Spironucleus muris in hamsters and rats may be subspecies, with relative host specificity. 

 

Toxoplasma gondii

 

1.  Prevalence:  rare

2.  Diagnosis: histology.  Cysts containing PAS-positive bradyzoites or clusters of tachyzoites in muscle and heart.

3.  Disease: Usually subclinical.  Early infection may have enlarged, edematous mesenteric lymph nodes with necrosis of ileal lamina propria, focal hepatitis, myocarditis, interstitial pneumonia, and later brain lesions (gliosis, perivasculitis, meningitis).  Tachyzoites in intestinal tissue, mesenteric lymph nodes, lung, spleen, brain, skeletal muscle etc. during early infection.  Cysts in central nervous system, skeletal muscle and cardiac muscle in chronic infection.

4.  Transmission: orofecal (cat feces containing oocysts).  Also cannibalism and vertical (in utero) transmission. 

5.  Duration: chronic

6.  Comment: T. gondii has a complex life cycle.  Oocysts shed in feces of cats, sporulate in the environment; sporozoites released after ingestion and invade intestine of intermediate host (mouse).  After invading cell, sporozoites differentiate into tachyzoites and replicate multiple generations.  Can infect virtually any cell type.  Immune response stimulates tachyzoites to differentiate into bradyzoites with a protective cyst wall.  Ingestion of tissue cysts by cat results in release of tachyzoites, invasion of intestinal epithelium, and differentiation into sexually replicating forms (microgametes and macrogametes), with formation of oocysts. 

 

NON-PATHOGENIC PROTOZOA

 

Tritrichomonas muris

Entamoeba muris

 

 

 

V.      HELMINTHS

 

A.   NEMATODES

 

Aspicularis tetraptera

Syphacia obvelata

(Syphacia muris)

 

B.   CESTODES

 

Cysticercus fasciolaris (Taenia taeniaeformis)

Rodentolepis nana, diminuta, microstoma

 

 

 

 

Aspicularis tetraptera,

Syphacia obvelata (Pinworms, oxyuriasis)

 

1.   Prevalence: high

2.  Diagnosis: ova in feces. Scotch-tape test for Syphacia. Adults in gut lumen. Aspicularis ova are symmetrical, Syphacia asymetrical.

3.  Disease: minimal or none. Mucosal invasion with focal inflammation can be seen in immunodeficient mice. Rectal prolapse attributed to heavy infestations. Syphacia deposits eggs around anus, Aspicularis does not.

4.  Transmission: orofecal. Ova very resistant to dessication and drift in air & dust. Pinworms are often the first to contaminate barrier-maintained mice.

5.   Duration: chronic. Immunity develops with age

6.  Comment: treatment controls, but seldom eradicates worms. Immune effects reported.  Syphacia muris (rat pinworm) has been found in a colony of Stat6 KO mice, but other knock out mice in colony (IL4 alpha, IFN-gamma, IL-10) were not affected.  Affected mice hosted very heavy parasite burdens in ceca.

 

Cysticercus fasciolaris (Taenia taeniaeformis)

 

1.   Prevalence: rare

2.   Diagnosis: gross, microscopic lesions

3.   Disease: strobilocercus in liver incidental finding in asymptomatic host

4.   Transmission: contamination of food and bedding with cat feces

5.   Duration: chronic

6.   Comment: rodent is intermediate host for cat tapeworm

 

Rodentolepis nana

R. diminuta

R. microstoma

 

1.   Prevalence: low in laboratory mice. Common in wild mice. Order of prevalence in wild mice listed above.

2.   Diagnosis: ova in feces, adults in intestine

3.  Disease: usually subclinical. Local enteritis or pancreatitis.  R. nana and R. diminuta in intestine. R. microstoma in bile/pancreatic ducts and duodenum.

4.   Transmission: All have arthropod intermediate host. Intermediate host for H. nana optional.

5.   Duration: chronic

6.  Comment: Formerly Hymenolepis.   R. diminuta and R. microstoma ova have polar filaments. R. nana adult is smallest of the three (dwarf tapeworm). Zoonotic hazard, especially with R. nana, as no intermediate host required (superinfection with local mucosal cycle).

 

 

VI.     ARTHROPODS

 

            A. MITES

Demodex musculi

Myobia musculi

Myocoptes musculinis

Radfordia affinis

 

                        Psorergates simplex

                        Ornithonyssus bacoti

 

  B. LICE

Polyplax serrata

 

C. FLEAS

 

Xenopsylla cheopsis

Nasopsyllus fasciatus

Leptopsylla segnis

 

Demodex musculi

 

1.  Prevalence: rare

2.      Diagnosis: skin scrapings and histosections

3.   Disease: usually subclinical, but dermatitis is being noted in various genetically altered mice, most recently auricular dermatitis in BALB-IL-13 KO mice.  Mites in follicular openings of the superficial dermis of dorsal thorax, often with no inflammation.

4. Transmission: contact

5.  Duration: chronic

6.   Comment: not reported in laboratory mice since 1917 until 1997, when it was found in a colony of transgenic mice with NK and T cell deficiency. Recognition of infestation is on the rise among genetically altered mice.

Has been recently seen in other immunodeficient mice on both east and west coasts. Affected mice harbor few mites, but more severely immunodeficient mice may harbor higher parasite numbers. 

 

Myobia musculi

 

1.   Prevalence: common

2.  Diagnosis: mites in fur, prefers fur of dorsal neck, shoulders. Single empodial claw on second pair of legs.

3.   Disease: often subclinical. Hypersensitivity can occur with ulcerative dermatitiis, pruritis, trauma and erosion of pinnae. Genotype-dependent (C57BL)

4.   Transmission: contact

5.   Duration: chronic, with immune-mediated equilibrium

6.   Comment: usually mixed infestations with other fur mites. Malnutrition, disease predisposes to overgrowth.

 

Myocoptes musculinis

 

I.    Prevalence: common

2.  Diagnosis: mites in fur, generalized distribution. Suckers on feet and pigmented third and fourth pair of legs.

3.   Disease: usually inapparent, but mild alopecia can occur.

4.   Transmission: contact

5.   Duration: chronic

6.   Comment: usually mixed infestations with other fur mites. Myocoptes dominates and is most common fur mite in laboratory mice.

 

Radfordi  affinis

 

1.   Prevalence: common

2.   Diagnosis: double embodial claws on second pair of legs.

3.   Disease: subclinical

4.   Transmission: contact

5.   Duration: chronic

6.   Comment: usually mixed infestation with other fur mites.

 

Psorergates simplex

 

1.   Prevalence: rare in laboratory mice, common in wild mice

2.   Diagnosis: 1 mm white nodules visible on underside of skin around head and neck

3.   Disease: follicular cysts filled with keratinized epithelium and mites at the epidermal junction.

4.   Transmission: contact

5.   Duration: chronic

6.   Comment: once common, now rare

 

Ornithonyssus bacoti 

 

1.   Prevalence: rare

2.   Diagnosis:  typical appearing lice in fur and environment

3.   Disease: anemia, debilitation and death

4.  Transmission: Ornithonyssus lives off host, thus diagnosis may require careful examination of the environment.

5.   Duration:  intermittent

6.  Comment: non-selective host range, including humans.  Animal handlers may manifest pruritic dermatitis.

 

Polyplax serrata

 

1..  Prevalence: rare

2.   Diagnosis: lice in fur, nits

3.   Disease: irritabilitiy, pruritis, anemia, dermatitis

4.   Transmission: contact

5.   Duration: chronic, with developing immunity

6.   Comment: sucking lice. Vector for E. coccoides.

 

Fleas  Rare. Xenopsylla most common in laboratory mouse colonies. Leptopsylla can serve as intermediate host for Hymenolepis.

 

 

May 2005