1.1 Taxonomy:

Order :	Rodentia	-
Suborder :	Myomorpha	-
Family :	Muridae	-
Genus :	Mus	-
Species :	musculus	-
Origin :	Asia (Old World)	-
Types of Mice :	Ecological Category	l. Germ free or Axenic
-	-	2. Gnotobiotic
-	-	3. Specific pathogen free
-	-	4. Conventional
-	Genetic Category	l. Random Bred
-	-	2. Inbred
-	-	3. F1 Hybrid offspring

1.2 Characteristics:

Long, hairless tail, timid, social, nocturnal animal. Prolific breeders, possess great genetic diversity, require little cage space, may become aggressive when housed individually, males housed together fight, may have an undesirable odor especially if males are maintained or if cages are dirty. Comprise 70% of all animals used annually in biomedical research in the United States.

1.3 Biological Data:

Age of puberty :	35 Days
Minimum breeding age:	60 days at 20-35 grams - male 50-60 days at 20-30 grams- females
Estrus cycles:	Polyestrus with minor seasonal variation
Duration of Estrus cycle:	4-5 days
Gestation:	17-21 days (average is 19) with lactation add 3-5 days
Litter size:	l-23 (average 10-12)
Number of litters:	6-10
Postpartum return to estrus:	14-28 hours after parturition
Birth weight:	l.5 grams
Weaned:	18-21 days at a weight of 10-12 grams
Weight at maturity:	20-40 grams - male 25-90 grams - female
Breeding life of male:	18 months
Breeding life of female:	10-12 months (6-10 litters)
Life Span:	2 years
Mating - colony:	Pair or colony of l male to 2-6 females
Recommended:	Temperature: 72oF (65o- 80oF)
Humidity:	30-70%
Body temperature:	97.5oF or 36.5o C
Mammae:	5 pairs - 3 thoracic and 2 abdominal (Mammae tissue extends over back and shoulders)
Heart Rate:	600/minute
Respiratory Rate:	163/minute
Housing (Minimum):	<10 gm Bwt 6 in2 floor space 10-15 gm Bwt 8 in2 floor space 15-25gm Bwt 12 in2 floor space >25 gm Bwt 15 in2 floor space Cage height - 5 inches
Diet:	Rodent chow fed ad libitum containing 18 to 24% crude protein and 4% crude fiber.
Feed Usage:	12 grams feed per 100 grams body weight, ad libitum.
Blood Sampling:	Orbital sinus, nick tail, nick toe, cardiac puncture*, tail vein puncture, jugular vein puncture, decapitation,* jugular incision* (* Not suitable for pet mice)
Anesthetics:	Sodium pentobarbital (IP): 60-90 mg/kg body weight (solution of 5 mg/ml in water containing 10% ethyl alcohol and 20% propylene glycol;administer in l ml tuberculin syringe.) Chlorpromazine (IM): 50 mg/kg + pentobarbital (IP 50 mg/kg) Ketamine: 44 mg/kg body weight (effectiveness questionable) Ether, Halothane, Methoxyflurane: Applied to gauze (ether causes profuse salivation).
Dental Formula:	2(I l/l C 0/0 P 0/0 M 3/3, incisors continually erupt)
Use in Research:	Genetics of tissue transplantations, nuclear cytology, embryology, nutritional studies, cancer research, genetic research, virology, radiation, infectious diseases, bioassay.
Hemogram:	RBC: 7.7 - 12.5 X 10 6/mm3 HCT: 39.4 - 52.2% Hb: ll.9 - 15.2 gm% WBC Total: 3.5 - 13.08 X 103/mm3 PMN: 4.6 -24.3% Lymph: 35.l - 93.3% Mono: 0.l - 3.4% Eos: 0 - 3.76% Bas: 0 - 0.3
Pseudopregnancy:	1-3 weeks, follows male exhaustion and sterility

1.4 NUTRITIONAL, REPRODUCTIVE, AND METABOLIC DISEASES OF THE MOUSE

Vitamin E Deficiency - muscular dystrophy

Vitamin D Deficiency - rickets

Amyloidosis

Poisoning - organophosphate, chloroform, streptomycin, procaine

Bite Wounds

Self Mutilation

Neoplasia - mice develop a great variety of tumors especially leukemia and mammary tumors

Alopecia

Dystrophic calcification

Weight loss

Malocclusion

Vaginal Discharge

Estrogen induced scrotal hernia

Infertility

Cystic Ovaries

Litter desertion or cannibalism

Dermatitis - non-specific, nasal -cage

Starvation or water deprivation 

1.4.1 BACTERIAL DISEASES OF THE MOUSE 

Tyzzer's disease

Bacillus piliformis - acute, enzootic disease with diarrhea, dehydration, debility and death occurring within 48 hours. 

Corynebacterium kutscheri

Characterized by emaciation, rapid respiration, nasal and ocular discharge, swollen joints, depression and hunched posture. 

Mycoplasma pulmonis

Respiratory infection 

Pasteurella pneumotropica

Labored respiration, weight loss. cutaneous abscesses, conjunctivitis, panophthalmitis, mastitis. 

Salmonella

Carrier states: S. typhimurium, S. enteritidis 

1.4.2 VIRAL DISEASES OF THE MOUSE 

Ectromelia

Mouse Pox Virus 

Epizootic Diarrhea of Infant Mice (EDIM)

Diarrheal disease of high morbidity and low mortality. 

Lymphocytic Choriomeningitis (LCM)

Usually asymptomatic but in the rare acute form LCM causes fatal meningitis of young mice

 Mouse Encephalomyelitis

Mouse polio 

Mouse Hepatitis (MHV)

Contagious enteric infection 

Sendai Virus

Stress or concurrent P. pneumotropica and Mycoplasma pulmonis infection precipitate devastating outbreaks 

1.4.3 PARASITES OF THE MOUSE

Ascariasis 

• Myocoptes musculinus - fur mite 
• Myobia musculi - fur mite 
• Radfordia affinis - fur mite
•  Psorergates simplex - follicular mite

 

Cestodiasis 

• Hymenileps nana - dwarf tapeworm (public health hazard) 
• Taenia taeniaformis (Cysticercus fasciculoris) - larval form in mice and rats

 

Sporozoans 

• Eimeria falciformis - intestinal coccidium 
• Klossiella muris - kidney coccidium

 

Flagellates 

• Hexamita muris - flagellate 
• Giardia muris - flagellate

 

Pediculosis 

• Polyplax serrata - blood sucking lice that transmits the agent of murine eperythrozoonosis

 

Oxyuridiasis 

• Syphacia obvelata - pinworm, perianal eggs - cellophane tape 
• Aspiculasris tetraptera - pinworm - flotation method  

 

1.5 References:  1. Fox, J.G., Cohen, B.J., and Loew, F. M.: Laboratory Animal Medicine; Chapter 3. Academic Press, l984. 2. Harkness, John E. and Wanger, J.E.: The Biology and Medicine of Rabbits and Rodents, Lea and Febiger, l983. 3. Simmons: M. L., and Brick, J.O.: The Laboratory Mouse, Prentice-Hall, Inc., l970. 4. Green, Earl L., ed.: Biology of the Laboratory Mouse, McGraw-Hill Book Co., l966. 5. Cook, M. J.: The Anatomy of the Laboratory Mouse, Academic Press. Inc. , l965. 6. USAF School of Aerospace Medicine, Brooks Air Force Base: The Mouse, Vol. XIX.

 REVISED: May, l986

1.6 SUMMARY OF PHEROMONE PRODUCTION IN MICE 

Olfactory stimuli provide a means of communication between animals. Substances producing these stimuli are known as pheromones. Pheromones are defined as substances, or mixtures of substances, which are produced to the exterior by an animal and may be received by a second individual of the same species in which they produce one or more specific reactions1. The term pheromone is derived from the Greek words "pherin" meaning to carry and "hormone" meaning to excite or stimulate2. Both signaling, and priming pheromones have been postulated as producing behavioral responses in mice3. Signaling pheromones include the fear substance, male sex attractant, female sex attractant, aggression-inducer, and aggression-inhibitor. Priming pheromones are the estrus-inducer, estrus-inhibitor, and adrenocortical activator. Wild mice react the same as laboratory mice to pheromone stimuli4.

Pheromones alter the normal estrus cycles of mice. Mice under regulated diurnal light cycles exhibit a relatively short estrus cycle of 4 to 6 days. If copulation or a similar stimulus does not occur, the short cycle reoccurs and is free of a luteal phase. Corpora lutea form but do not secrete significant levels of progesterone. Organized corpora lutea form if sterile mating takes place and the estrus cycle is extended to 10 to 15 days. These cycles are called pseudopregnancies and occasionally occur spontaneously. Normal pregnancies in mice require 19 to 20 days with implantation occurring on the 5th day. After delivery, postpartum estrus and ovulation occur and mating may take placel. Changes in the estrus cycles of mice, stimulated by pheromones, have been termed the Bruce effect, Lee-Boot effect, and Whitten effect.

Pheromones produced by both male and female mice influence their reproductive activities. The Bruce effect is a block of pregnancy occurring when a recently mated female is placed with a strange male. Pheromones from the strange male produce this effect. Pseudopregnancy, or anestrus, detected after grouping female mice is caused by female pheromones and is called the Lee-Boot effect. The Whitten effect occurs when previously grouped females mice are paired with males resulting in a higher incidence of mating the third night after pairing. This effect is produced by pheromones from either the male or his excreta. An understanding of pheromones is necessary for optimum care and management of laboratory mice. 

1.7 GLOSSARY OF GNOTOBIOTIC TERMS 

(From: Handbook of Laboratory Animal Science, Vol. I, 1974. CRC Press)

 A number of attempts have been made to systematize the terminology used in gnotobiotic technology, but no single system is universally accepted. In this publication the nomenclature has been limited to terms that, by general usage, are familiar to and understood by most workers in the field. 

GNOTOBIOTIC

A word derived from Greek gnotos and biota, meaning known flora and fauna. 

GNOTOBIOTE (GNOTOBIOTIC ANIMAL)

On of an animal stock or stain derived by aseptic caesarean section or sterile hatching of eggs that is reared and continuously maintained with germfree technics under isolator conditions and in which the composition of an associated fauna and flora, if present, if fully defined by accepted and current methodology. 

GERMFREE ANIMAL (AXENIC ANIMAL)

A gnotobiote that is free from all demonstrable associated forms of life, including bacteria, viruses, fungi, protozoa, and other saprophytic or parasitic forms. Since criteria for establishing "germfreeness" depend on currently available diagnostic tests, animals now designated as germfree may possibly in the future be found to harbor one or more viable agents. 

DEFINED FLORA ANIMAL

A gnotobiote maintained under isolator conditions in intentional association with one or more known types of micro-organisms. Such terms as "monoinfected," "monocontaminated," "monoassociated," and "polycontaminated" have been employed to describe this type of gnotobiote. Of these, the terms "monoassociated" and "polyassociated" are preferable for describing intentional, rather than accidental, association with microbes. 

CONVENTIONAL ANIMAL

An animal with an uncontrolled flora, reared under open animal room conditions in association with other animals of the same type. 

CONVENTIONALIZED ANIMAL

An animal originally born or delivered under gnotobiotic conditions, which has subsequently been intentionally provided with the microflora of a conventional animal. 

EX-GERMFREE ANIMAL

An animal born or delivered under germfree conditions, which, accidentally or intentionally, acquired a microbial flora.

1.8 Nomenclature for Outbred animals 

1.9 Nomenclature for Inbred animals   

1.10 Ear marking Cod 

1.11 NOMENCLATURE FOR INBRED ANIMALS  

1.12 MOUSE DISEASES 

1.12.1 OBJECTIVES 

• l. Know the possible etiologies of diarrhea and/or enteritis in mice. Be able to arrive at diagnosis of each. Give a method of treatment or control where applicable.
• 2. Know the group of infectious organisms which can cause respiratory disease. Give pertinent clinical signs and gross pathology. Know methods to arrive at a diagnosis. Give method of treatment or control.
• 3. Know the characteristic lesions of mousepox and how to control it.
• 4. Know how to examine mice for endo- and ectoparasites. Give method of treatment or control for each parasite.
• 5. Know the causes of alopecia in mice and how to diagnose. Give a method of treatment or control where applicable.
• 6. Know which murine diseases are public health hazard.
• 7. Know the symptoms and lesions of Corynebacterium kutscheri.

1.12.2 BACTERIAL DISEASES

1.12.2.1 Corynebacteriosis (Murine Pseudotuberculosis)

First isolated from mice in Germany by Kutscher in 1894.

A. Etiology:

Corynebacterium kutscheri = a gm (+) short rod.

B. Transmission:

The bacteria is spread by aerosol or perhaps by direct contact with excreta. Since a carrier state or latent infection is the predominate form of infection, overt disease or latent infection is precipitated by physiological stressors (disease, pregnancy, corticosteroids).

C. Clinical Signs:

Once stressed, the mouse may exhibit the typical "sick mouse syndrome" (rough hair coat, hunched posture, anorexia) accompanied with dyspnea and oculonasal discharge. Occasionally subcutaneous abscesses or septic swollen joints may occur.

D. Gross Pathology:

Large often coalescing abscesses containing white caseated purulent material are present in the lungs (hence the name pseudotuberculosis). Multiple white foci of necrosis primarily in the liver and kidney, subcutaneous and joint abscesses represent the showering and lodgement of septic emboli.

E. Diagnosis:

The presence of focal necrosis of highly vascular viscera (especially kidney) suggests corynebacteriosis. Culture of necrotic foci or abscesses provides the definitive diagnosis. Serological tests such as tube agglutination and ELISA identify diseased and carrier animals.

F. Treatment:

No treatment has been proposed.

G. Control:

Identification of the carrier animals (by cortisone provocation- 10 mg/animal or serological test) and elimination from the colony. Since rats are also known to carry the infection, mice and rats should not be housed in the same room nor should common equipment (water bottles, cages) be shared unless thoroughly sanitized.

1.12.2.2 Salmonellosis

First isolated by Loeffler in 1892 during an epidemic in a laboratory mouse colony. New CDC classification is Salmonella enteritidis var. typhimurium.

A. Etiology:

Salmonella enteritidis var.typhimurium = a gm (-) toxin producing, lactose (-), enteric bacterium.

B. Transmission:

Fecal-oral; food, water and bedding may be contaminated by infected feces from wild mice.

C. Clinical Signs:

Disease in susceptible colonies may be manifested only as acute death with moderate morbidity and high to sporadic mortality in weanlings and females in late gestation. Diarrhea may or may not be present. Carrier states follow overt disease and may be manifested in breeding colonies as chronic low fertility, fetal reabsorption, or abortion. Active disease is characterized by ruffled fur, dull appearance, anorexia, increase water intake, mucoid and/or occasionally bloody stool.

D. Gross Pathology:

In acute deaths, the spleen may be enlarged 2 to 3 times normal size. In subacute infections, multiple white to yellow foci occur in the liver. Lesions in the small intestine consist of mucosal congestion and edema with thrombosis of the mesenteric vasculature.

E. Diagnosis:

The history, gross lesions and presence of wild mice are suggestive of salmonellosis. Histopathological examination may reveal multifocal necrotizing hepatitis and splenitis. Culture of liver and spleen in acute cases and feces and homogenates of the ileum (more consistent recovery in subacute cases) on selective media such as selenite, brilliant green and MacConkey's agar or gram negative broth with serotyping of the isolate provides the definitive diagnosis.

F. Treatment:

Since the carrier state has not been successfully treated with antibiotics, elimination of the colony is suggested. Repopulate with caesarean derived stock.

G. Control:

Aggressive sanitation procedures should be aimed at preventing contamination of food, bedding and water, prevention of exposure to wild mice (vermin control) and proper disinfection of cages and watering equipment.

H. Public Health Significance:

Humans ingesting Salmonella enteritidis var. typhimurium contaminated food or water may experience a transient diarrhea. Infects personnel.

1.12.2.3 Tyzzer's Disease:

First report was published by Ernest Tyzzer of Harvard in 1917.

A. Etiology:

Bacillus piliformis = a gm (-) obligate intracellular rod. Forms subterminal spores and is motile by peritrichous flagellae.

B. Transmission:

Fecal-oral route by ingestion of spores. Predisposing factors to disease include age (commonly 3 to 7 weeks of age) and physiological stresses such as concurrent disease, experimental manipulations, poor housing conditions, or corticosteroid administration.

C. Clinical Signs:

Death is often the only indication of infection. Anorexia, hunched posture, rough hair coat, and diarrhea may precede death.

D. Gross Pathology:

Multiple yellowish white foci of necrosis in the liver and serosal edema and hemorrhage in the ileocecocolic region of the gut are prominent lesions.

E. Diagnosis:

Since the organism cannot be propagated on artificial media, diagnoses are made by demonstration with stains of the bacillus in the hepatocytes bordering necrotic liver foci. A silver stain is preferred. However, Giemsa or PAS stains may be used. Indirect fluorescent antibody test is useful for survey purposes. Cortisone provocation test can also be used to detect latent infection.

F. Treatment:

Oxytetracycline at O.l mg/ml water for 30 days has been reported to abate an epizootic. Treatment may interfere with research.

G. Control:

Avoidance of stress and strict sanitation help prevent outbreaks. Decontaminate the infected facilities using O.3% Sodium Hypochlorite since this concentration is sporicidal.

1.12.2.4 Murine Colonic Hyperplasia:

First report was described by Brennan et al. 1965, from an outbreak of diarrhea in laboratory mice.

A. Etiology:

Citrobactor freundii strain 4280 = a gm (-) pleomorphic rod.

B. Transmission:

Fecal-oral route, affects preweaning, and recently weaned pups.

C. Clinical Signs:

Affected mice look sick and may excrete soft feces. Mortality is variable; but may reach up to 60%, death often ensues in 3-5 days. Survivors often have rectal prolapse (15% incidence) because of straining. Adults show no clinical illness.

D. Gross Pathology:

The colon, especially the descending portion, has a greatly thickened mucosa which increases its relative size.

E. Diagnosis:

The crypts of the colon are often greatly elongated up to 3 times normal with active cellular mitoses at the base of the crypts and little inflammatory reaction. The bacteria may be visualized attached to the surface epithelium. Culture can be difficult but isolation and typing of the particular strain are essential to a definitive diagnosis.

F. Treatment:

The disease is contagious but self-limiting. Rectal prolapses can occur after Citrobacter freundii has been eliminated from the gut. The rectal prolapse may be corrected by using a moistened micro cotton swab. Neomycin and tetracycline given in drinking water reduces the loss during an outbreak, but does not eliminate the infection.

G. Control:

Prevention of fecal contamination by strict sanitation is important in controlling the disease. An infected colony may require depopulation and repopulation using cesarian derived stock.

1.12.2.5 Mycoplasmosis:

Has been known in mice and rats since 1915, but Koch's postulates were fulfilled first in mice in 1966, and in rats in 1969.

A. Etiology:

Mycoplasma pulmonis = a microorganism lacking a cell wall. They are the smallest and simplest self-replicating prokaryotes.

B. Transmission:

Aerosol, intrauterine (congenital or vertical) and direct contact are 3 known modes of transmission.

C. Clinical Signs:

Most infections are subclinical with the organism carried in the oropharynx. The acquisition of primary viral or bacterial respiratory pathogens activate subclinical mycoplasmal infections. Early signs of overt disease include an oculonasal discharge and otitis media (upper respiratory tract infection). As the organism travels down the respiratory tract, labored breathing, anorexia, hunched posture, etc. occur. "Chattering" sound in mice can be heard in the room.

D. Gross Pathology:

In the upper respiratory tract, a purulent discharge may be found on the nasal mucosa and within the tympanic bullae. This purulent exudate can be found in the trachea and bronchi causing yellow foci in the parenchyma, due to distended airways containing mucous or exudate (bronchiectasis) and red to gray areas of consolidation.

E. Diagnosis:

Histological examination of lungs reveal a purulent bronchopneumonia with moderate hyperplasia of the normally scant peribronchial lymphoid aggregates. Microbiological surveys usually identify Mycoplasma pulmonis along with other respiratory pathogens such as Corynebacterium kutscheri, Pasteurella pneumotropica, Streptococcus pneumoniae and Sendai virus. The media needed for primary Mycoplasma recovery must contain swine or horse serum and yeast extract supplementation. An ELISA is commercially available for serological screening of subclinical Mycoplasma pulmonis infections in mouse and rat colonies. FA can also be used to identify the organism on tracheobronchial sections.

F. Treatment:

The overt disease is just suppressed by antibiotic therapy. Oxytetracycline (0.l mg/ml water), tetracycline (3-5 mg/ml water), sulfamerazine (0.02% in water or l mg/4 gm food), chloramphenicol (30 mg/kg b.i.d.), and tylosin (l0 mg/kg s.i.d.) for 5 days have all been reported to reduce mortality. The carrier state is not affected.

G. Control:

Since intrauterine infection can occur, even cesarian derivation may perpetuate the infection. Rigid sanitary measures are essential even in the face of a disease outbreak. Since rats are known carriers, they should never be housed with mice. Ammonia levels in the cages and rooms should be kept to a minimum as high levels may predispose to Mycoplasma infection.

H. Other Species of Importance

1.12.2.5.1 Mycoplasma neurolyticum:

Although not common, causes a conjunctivitis in mice. Also causes "rolling disease" in mice.

1.12.2.5.2 Mycoplasma muris:

A new species isolated from the vagina of pregnant mice. Significance unknown.

1.12.2.5.3 Mycoplasma collis:

A new species isolated from the nasopharynx of rats and mice in 1983. Significance unknown.

1.12.2.6 Pasteurellosis:

First reported in 1950 as a respiratory tract pathogen of major importance in mice.

A. Etiology:

Pasteurella pneumotropica = a gm (-) short pleomorphic rod with bipolar staining properties.

B. Transmission:

Aerosol, fecal-oral and contact with infected secretions (including venereal transmission) have been reported. The bacteria can be consistently isolated from the oropharynx of exposed mice.

C. Clinical Signs:

Conjunctivitis and panophthalmitis in epidemic proportions have occurred in weanling mice. An upper respiratory infection is manifested by an oculonasal discharge and as the infection progresses, dyspnea may occur. Subcutaneous abscesses, mastitis, metritis and accessory sex gland abscesses have also been observed.

D. Gross Pathology:

The infected ocular structures range from a mucopurulent conjunctivitis to abscessation of the orbit and underlying Harderian gland. A purulent discharge may cover the mucosa of the nose, trachea, and bronchi. The lungs may be mottled tan to red and appear firm and wet. The abscesses of the subcutis, mammary gland, and accessory sex glands are often encapsulated and contain thick white purulent material which may drain to the exterior.

E. Diagnosis:

Culture of the ocular, skin or glandular tissues may reveal pure cultures of Pasteurella pneumotropica. Mixed infections with Mycoplasma pulmonis or Streptococcus pneumoniae or Sendai virus with Pasteurella pneumotropica commonly occur. P. pneumo-tropica is only occasionally isolated in pure cultures.

F. Treatment:

Many isolates are resistant to tetracycline. Ampicillin (5 mg/lb) has been reported to eliminate the carrier state. Chloramphenicol (30 mg/kg b.i.d. for 5 days) has also been used.

G. Control:

The same preventative measures for control of Mycoplasma pulmonis applies to Pasteurella pneumotropica. 

 

1.12.2.7 . Mycobacterium avium-intracellulare:

Natural infection in mice was reported in a commercial facility in 1983. The source was contaminated water. Causes gross and histopathologic lesions like mammalian tuberculosis.

 

1.12.2.8 Pseudomonas aeruginosa:

Opportunistic pathogen or through contaminated water. Causes "rolling disease" in mice.

1.12.2.9 Klebsiella pneumoniae:

Opportunistic pathogen in mice.

1.12.2.10 Chlamydia trachomatis:

Has caused pneumonitis in mice.

1.12.2.11 Streptococcus pyogenes:

Has caused cervical lymphadenitis in mice.

1.12.2.12 Staphylococcus aureus:

Has caused dermatitis in mice. Many rodent colonies have infection but no overt disease. Also all injuries of skin are infected by Staphylococcus aureus.

A. A few examples are:

• l. Ulcerative dermatitis in mice - mostly face, neck, ears, and forelegs.
• 2. Facial abscesses in immunocompetent mice - extra-orbital tissues, facial muscles, etc.
• 3. Orbital and facial abscesses in athymic nude mice - purulent lesions mostly.
• 4. Preputial gland abscesses - preputial glands are enlarged.
• 5. Self mutilation of penis - Common in young males used in harem breeding. Swelling of sheath occurs, which leads to incomplete protrusion of the penis. The penis of most males is mutilated so severely that the os penis protrudes from the surface. Staph. aureus in pure culture has been isolated. 

1.12.3 VIRAL DISEASES

1.12.3.1 Sendai Virus

A. Etiology:

RNA paramyxovirus. Family Paramyxoviridae.

B. Transmission:

Highly contagious, spread by aerosol and direct contact. Infections are usually enzootic in a colony and are reported to be maintained by horizontal infection in young mice. Intrauterine transmission after IV injection of pregnant mice has been reported.

C. Clinical Signs:

May see sick mice with labored breathing and decreased fecundity. This virus is immunosuppressive and may predispose to secondary bacterial infections, especially Mycoplasma pulmonis.

D. Gross Pathology:

The lungs of affected mice may be mottled; red and tan foci in the parenchyma and exudate in the major airways may be seen.

E. Diagnosis:

Histological examinations reveal characteristic interstitial pneumonia with perivasculitis, peribronchiolitis hyperplasia of alveolar macrophages, and foci of alveolar necrosis with a neutrophilic infiltrate. Squamous metaplasia of the bronchial epithelium is highly suggestive of this infection. A bronchial exudate may be seen. Complement fixation and HAI can be used to determine antibody titers. ELISA is most sensitive as has been recently shown.

F. Treatment:

The disease is difficult to treat. A vaccine is commercially available and is showing relative success. It is formalin killed-duck embryo origin vaccine. A single O.l ml dose given IP gives approximately 7 months protection.

G. Control:

Cessation of all breeding activity for 60 days followed by vaccination may abate an epizootic.

 

1.12.3.2 Lymphocytic Choriomeningitis (LCM):

A. Etiology:

Arenavirus - RNA virus, Family - Arenaviridae.

B. Transmission:

In utero or perinatal infections (within l day postpartum) produce a subclinical persistent infection. Virus is continually shed in urine and saliva but no antibody titer is produced. If infected at any other time, antibody production occurs.

C. Clinical Signs:

Usually there are no clinical signs. It is rare to see meningitis; occasionally convulsions, decreased growth, and reluctance to move may be seen. This is often termed a persistent tolerant infection (PTI). These mice later develop "late disease" which consists primarily of immune complex glomerulonephritis.

D. Gross Pathology:

Gross lesions vary from none to focal visceral necrosis and splenomegaly.

E. Diagnosis:

Histological examination of the brain reveals lymphocytic infiltration of the meninges, choroid plexus, and in submeningeal and subchoroid perivascular spaces. Complement fixation tests may reveal serum antibodies. Infected neural tissues can be injected into suckling mouse footpad (get swelling in 5-9 days) or cerebrum (neurological signs) to confirm diagnosis. Fluorescent antibody testing of livers harvested from mice is the method of choice. An ELISA test has been developed, and appears to be more sensitive than complement fixation test.

F. Treatment: None 

G. Control:

Eliminate colony since vertical transmission of the virus makes control measures useless.

H. Public Health Significance:

CDC reports human LCM infection linked primarily to exposure to infected hamsters. Mouse LCM is also a zoonotic disease (?)

 

1.12.3.3 . Mouse Hepatitis Virus:

(MHV) - Highly contagious and extremely ubiquitous in laboratory mice.

A. Etiology:

Coronavirus, - RNA virus - Family Corona-viridae. Several MHV strains display tropisms for different tissues but all exhibit hepatotoxicity.

B. Transmission:

Fecal-oral, aerosol, and in utero routes of infections have been reported.

C. Clinical Signs:

Symptomatology is age and strain dependent. In suckling mice, watery diarrhea with high mortality occurs; this disease used to be called Lethal Intestinal Virus of Infant Mice (LIVIM). In weanling mice, obstipation has been reported. Older mice show hunched posture, rough hair coats, weight loss, and variable death rate. Athymic nude mice exhibit a progressive wasting disease.

D. Gross Pathology:

In suckling mice, theintestinal tract will be flaccidly distended with gaseous contents. Obstipated weanlings may have cecal and/or rectal impactions with firm dry feces. Older mice exhibit primarily multiple white liver foci. The livers of infected nude mice have a hob-nail, nodular appearance.

E.Diagnosis:

Histopathological examinations of neonatal and weanlings intestinal tracts reveal syncytial cell formations of the intestinal epithelial cells, also shortening of the intestinal villi is an important finding. Focal coagulative liver necrosis is seen in all age groups and strains; often syncytiated hepatocytes are present around necrotic centers. In nude mice, intestinal epithelial cells, hepatocytes and vascular endothelial cells undergo syncytial cell formation. Hepatic fibrosis is a prominent finding. Tests to aid in diagnosis include complement fixation and FA of affected tissues. Recently ELISA has been found to be superior to complement fixation test.

F.Treatment: None

G.Control:

Either tolerate infection in the colony (it eventually becomes endemic) or restock with clean animals. If it is necessary to maintain an infected colony, use filter tops to contain the infection within the cage itself. In the case of nude mice, rigid aseptic housing conditions approaching germ free standards are often necessary to prevent viral exposure and infection.

 

1.12.3.4 .Epizootic Diarrhea of Infant Mice (EDIM)

A.Ecology:

Rotavirus - RNA virus - family Reoviridae

B.Transmission:

Fecal-oral, direct contact, and aerosol. The adult mice are unapparent viral carriers and shed the virus to the their susceptible young.

C.Clinical Signs:

A watery yellow diarrhea develops in 14-17 day old or suckling mice. Feces often dry on the perineum causing obstipation and death. Surviving mice have stunted growth. 

D.Gross Pathology:

The intestines contain yellow gaseous contents. If a dried perineal fecal plug is present, the intestinal tract may be dilated with the gaseous contents. Histologically there is atrophy of the intestinal villi in the caudal 2/3 of the small intestine.

E.Diagnosis:

The clinical signs and positive serology by serum neutralization tests or by FA on infant mouse intestinal cells allow definitive diagnosis. CF test can be used to survey the rotaviral antibodies in the colony.

F.Treatment:

Remove perianal fecal masses with warm water soaks.

G.Control:

To prevent spread of the virus in a colony, individual cage filter covers may be used. The disease is most severe in mice born to nonimmune dams. Multiparous dams clean up infant feces and produce antibodies to protect future litters.

 

1.12.3.5 Mousepox:

First recognized by Marchal in England in 1930.

A. Etiology:

Ectromelia virus - a DNA poxviridae family, related to the vaccinia subgroup. It is the largest of the DNA viruses. [Ectro = loss; melia = limb; means loss of limb(s)]

B. Transmission:

Fecal-oral, urine contamination or by direct contact. Infections are usually latent with viral replication in the intestinal epithelial cells. Severity of disease is dependent on the mouse strain. (ex. DBA strains highly susceptible, and C57BL strain highly resistant).

C.Clinical Signs:

In acute disease, there is high morbidity and high mortality with affected animals exhibiting hunched posture, conjunctivitis and facial swelling. Subacute to chronically infected animals develop a cutaneous vesicular body rash which often progresses to swelling, necrosis and sloughing of the extremities. Deaths are sporadic. Necrotic amputation of limbs (Ectromelia) and tails may be seen in mice which survive acute disease.

D.Gross Pathology:

Lesions from animals dying from acute disease consist of visceral congestion, splenomegaly, white necrotic foci in the liver, and peritoneal exudate. Focal liver, spleen and pancreas necrosis, erosive enteritis and vesicular pox lesions on extremities can be found.

E.Diagnosis:

Although clinical and gross pathology signs are highly suggestive of the disease, histological demonstration of intracytoplasmic inclusion bodies in epithelial cells surrounding vesicular ulcers, in small intestinal cells and in pancreatic cells are necessary to confirm the diagnosis. Serological tests utilizing HAI and ELISA as well as FA of tissues support a histopathological diagnosis. Differential diagnosis should include fight wounds, bite lesions, loss of limbs due to Streptobacillus moniliformis or Mycoplasma arthritidis and trauma due to cage injury.

F.Treatment: None

G.Control:

If the animals are readily available commercially, exterminate the infected colony and formalin sanitize the facility (means fumigate). Valuable exposed animals and their offspring may be vaccinated with the IHD-T strain of vaccinia virus, by scarification at the tail base. Sentinel animals (known susceptible disease free mice) are routinely placed in the colony to test the efficacy of vaccination.

1.12.3.6 .Other Viral Diseases:

• l.Pneumonia Virus of Mice (PVM): Paramyxoviridae - significance low.
• 2. K virus: Papovaviridae - significance low.
• 3.Mouse Papule Virus: unclassified virus - significance low.
• 4.Reo 3: Reoviridae - Little evidence of natural disease - significance low.
• 5. Mouse Adeno virus: Adenoviridae - significance low.
• 6.Mouse encephalomyelitis virus: Picornaviridae - mouse polio, flaccid paralysis of hindleg, significance low.
• 7.Lactic Dehydrogenase Elevating virus (LDE): Togaviridae - no natural disease, tumor contaminant, significance low.
• 8.Minute Virus of Mice (MVM): Paroviridae - virus occurs as contaminant, significance low.
• 9.Polyoma virus: Papovaviridae - experimental infection only. No natural disease, significance low.
• 10.Mammary Tumor virus (MTV): Retroviridae - Type B viral particle. Mostly female mice affected. C3H and A strain highly susceptible.
• ll.Mouse Thymic virus: Herpesviridae - contaminant mainly.
• 12.Murine Leukemia Virus: Retroviridae - Type C viral particle. Spontaneous disease in certain strains (e.g. AKR) of mice.

1.12.4 FUNGAL DISEASES

1.12.4.1 DERMATOPHYTOSIS

A.Host:

Mice, rats, guinea pigs and rabbits.

B.Etiology:

Trichophyton mentagrophytes. Very common. Occasionally Microsporum species. T. mentagrophytes infects humans.

C.Transmission:

Direct contact with spores or poor husbandry.

D.Clinical Signs:

Tail lesions are common in mice. Facial hair loss, erythema, scaling of skin, (ring worm lesions) etc.

E.Diagnosis:

• 1.Examine skin scrapping after 10% KOH digestion.
• 2.Culture on fungal media.

F.Treatment:

• 1.Topical treatment; use Conofite, Nilstat, Tinactin
• 2.Systemic treatment; give injectable or oral Amphotericin B, Gresiofulvin or Mycostatin.

'USE CARE (WEAR GLOVES) WHEN HANDLING SUCH ANIMALS'

1.12.5 PARASITIC DISEASES

1.12.5.1-Mites and Lice

A.Mouse Mites

1.Etiology:

Mycoptes musculinus, Myobia musculi, and Radfordia affinis are common fur mites. Psorergates simplex, the follicular mite, are rarely seen. Adult mites have four pairs of legs and lice have three pairs of legs.

2.Transmission:

Direct contact. Fur mites are usually host specific.

3.Clinical Signs:

Usually no clinical signs are observed. Black haired mice are thought to have an allergic sensitivity to the mites manifested by pruritus, alopecia progressing to excoriation and ulcerative dermatitis leading to disfigurement.

4.Diagnosis:

On live mice, plucking hairs from the pelt and examination under a scope may reveal the eggs (laid on the hair shaft) or the mites. If a recently killed mouse is cooled (in a refrigerator for 30 minutes) and allowed to warm up to room temperature, the mites will crawl up to the tips of the hairs, looking like white specks. If an animal has been dead for a while, the mites may have migrated to another host.

5.Treatment:

A vapona strip (No PestR, Dichlorvos) placed above the cage or in the room will control infestations. The adults and weanlings can be dusted with silica dusts, pyrethrin dusts, or can be dipped in a 2% malathion solution.

6.Control:

Regular examinations and treatments may eventually rid the colony of mites.

1.12.5.2 Mouse Lice

Polyplax serrata: sucking lice, vector of Eperythrozooncoccoides. Significance low.

1.12.5.3 .Cestodes

A. Hymenolepis spp.

• 1.Hymenolepis nana (Dwarf tapeworms) and Hymenolepis diminuta.
  • a.Transmission: Hymenolepis nana and Hymenolepis diminuta can be transmitted by an indirect mode with cockroaches, grain beetles or fleas as intermediate hosts. Hymenolepis nana can also be transmitted by direct ingestion of hexacanth ova or by autoinfection in which the entire life cycle occurs in the small intestine without ingestion of ova (complete life cycle in 14-16 days).
  • b.Clinical Signs: Usually there are no external signs of infection. However, catarrhal enteritis, diarrhea, emaciation and chronic weight loss may occur with heavy infestations.
  • c.Gross Pathology: Hymenolepis nana adults range from 15-40 mm long and less than l mm wide and have an armed rostellum. Hymenolepis diminuta adults range from 20-60 mm long and 3-4 mm wide without hooks on scolex. Often these tapeworms migrate up the pancreatic and biliary ducts.
  • d.Diagnosis: Visualization of the tapeworm in the small intestine during necropsy, recovery of hexacanth ova by fecal flotation, microscopic visualization of segmented parasites or encysted larvae in histological sections of the small intestine.
  • e.Treatment: Niclosamide (YomesanR) at 10 mg/100 gm body weight should be given in two treatments at 7 day intervals.
  • f.Control: Cockroaches should be eliminated and infected animals treated or eliminated from the colony.
  • g.Public Health Significance: Humans are susceptible to Hymenolepis nana infections; since autoinfection can occur, a heavy parasite load may quickly develop.

B. Taenia taeniaformis

Mice serve as intermediate hosts for cat tapeworm Taenia taeniaformis. The cysticercoid cyst (Cystecercus fasciolaris) embeds in the liver and causes no clinical effects. Infection occurs when mice ingest ova in cat feces; fecal contamination of mouse food or bedding can occur. No treatment is necessary but feline fecal contamination should be prevented.

 

1.12.5.4 Protozoa

A.Spironucleus muris (Hexamita) - A flagellated protozoa that dwells on the mucosal surface of the small intestine.

1.Transmission:

Ingestion of infective cysts is the primary mode of transmission. A carrier stage occurs in adults.

2.Clinical Signs:

Weanling mice (3-6 weeks age) appear to be most susceptible. Heavily infected mice are usually smaller in size, depressed and have abdominal distension. A "sticky" fecal mass may be seen on the perineal area. Dehydration and anorexia follow with moderate mortality rate (0-25%).

3.Gross Pathology:

The small intestines are often dilated and filled with gassy catarrhal fluid contents. The mucosa may be reddened. Autolysis rapidly ensues.

4. Diagnosis:

Direct smears of the contents reveal fast darting protozoa. Histological examination of the small intestine will reveal the protozoa in the crypts and along the surface of the villous epithelium. Stain with Periodic Acid Schiffs or silver methods.

5.Treatment:

Dimetridazole (Emtryl is trade name; l% solution or l gm/l drinking water) has been reported to reduce mortality.

B.Tritrichomonas spp. and Giardia spp. - Pathogenic flagellated protozoa that occurs in the small intestine.

NOTE: Nonpathogenic flagellates occur in cecum, colon and small intestine.

1.Transmission: The main route of infection is ingestion of the organism which is passed in feces of the infected animal.

2.Clinical Signs:

No clinical signs have been attributed directly to these organisms. Diarrhea is often associated with both organisms; however, it is believed that the diarrheal state merely provides them with the optimum growth environment.

3.Gross Pathology:

No Specific pathology, Tritrichomonas is most commonly found in the lower small intestine and cecum, while Giardia is found primarily in the jejunum.

4.Treatment:

No specific treatment, and in colony situations, none is attempted. Lead arsenate given per os at a ratio of 0.5% in feed for l to 3 days will eliminate Giardia muris but it is toxic.

5.Control:

Colonies maintained behind a barrier and derived via cesarian section are usually Giardia and Tritrichomonas free.

C.Eimeria falciformis:

Mouse coccidia present in large intestine. Infection by sporulated oocysts. Treatment is by ordinary coccidiostats.

D.Entamoeba muris:

Nonpathogenic and found in cecum and colon.

E.Klossiella muris: Kidney Coccidia of mice. Kidney is sometimes enlarged.

 

1.12.5.5 Oxyurids

A. Syphacia obvelata and Aspicularis tetraptera: Both are called "Mouse Pinworm." Syphacia occurs in cecum and colon of the host, whereas, Aspicularis tetraptera occurs only in the colon of the host.

1.Transmission:

Syphacia obvelata female deposits eggs in the perianal region, while, Aspicularis tetraptera deposits eggs in the colon which enter into the feces. Transmission of infection occurs via ova ingestion. The eggs are very light and have been shown to aerosolize, resulting in widespread exposure.

2.Clinical Signs:

No signs are usually seen. It has been reported that heavy parasite loads may to rectal prolapse or perianal irritation. heavy parasitism may affect the immunocompetency of the animal.

3.Gross Pathology:

The pinworms are easily as white hairlike nematodes in the cecum or colon.

4.Diagnosis:

Direct exam. of cecal or colonic contents, fecal flotation, and tape (cellophane tape technique) test of the perianal region will identify adults and eggs, respectively. An Aspicularis tetraptera infection will be missed by tape test alone.

5.Treatment:

If treatment is desired, piperazine (4-7 mg/ml water) for 3-10 days is effective. Karo syrup can be added to the solution if the mice refuse to drink it.

6.Control:

Prevention and control of infection are often difficult. Rigid sanitary procedures, use of filter tops to prevent aerosol transmission and regular ova examinations with treatment may control the parasitism. Routine disinfection of animal facilities will not destroy pinworm ova.

1.12.6 MISCELLANEOUS DISEASES

1.12.6.1 Alopecia

1.12.6.2 Barbering

"Whisker-Trimming", and Hair Nibbling"

For some reason (possibly boredom or overcrowding) a dominant cage mate mostly female mouse may develop a fur-chewing vice and chew the hair off a cagemate or her litter. This usually involves the hair over the nasal and orbital regions. The only cure for barbering, if the client considers it a problem, is to separate the animals.

1.12.6.3 Fight Wounds

Bite Wounds in weanling mice, Bite Wounds in adults mice ( BALB/C, SJL/J strain common).

Mice (particularly males) may fight and inflict severe wounds upon each other. These usually are located on the face, back, rump, and genital areas. If tail biting occurs, the tail may become gangrenous and slough. The wounds may become infected and develop into abscesses. These may be treated by lancing and flushing with a tamed iodine or antibiotic solution. Injectable antibiotics may also be given, but it should be noted that Streptomycin is toxic to mice (the mechanism of toxicity is unknown) so Pen-strep combinations should not be used. Penicillin alone is nontoxic (recommended dose = 40,000 U/kg daily for 5-7 days IM). Prevention is by separating the offending animals.

1.12.6.4 Muzzle Alopecia

Mice housed in cages covered with a stainless steel cover in which holes have been punched for ventilation often show muzzle alopecia. The act of pushing the muzzle through the holes will break off the whiskers and hairs and can produce a superficial dermatitis. Replacement of the hole-punched lids with wire-bar tops will alleviate the source of the problem.

1.12.6.5 Otitis Media

or Self-Mutilation associated with Otitis Media

Otitis media has been reported to result in enough irritation to cause the animals to scratch the base of the ears with the hind feet. The scratching can lead to excoriation and ulceration of the neck and inoculation of the wounds with environmental bacteria contaminating the feet. The resultant dermatitis evokes a more intense scratching reflex until a large ulcerative pustular dermatitis results from the self-mutilating activity. Parenteral antibiotic therapy appears to be of little help for the otitis media or the dermatitis. Clipping of the toenails or amputation of the first phalanx of the digits of the hind feet will allow resolution of the dermatitis whether treated or not. Certainly the value of the animal will dictate the decision to treat or eliminate.

1.12.6.6 "Ring Tail"

This condition has also been reported in mice and the South African white tailed hamsters. Characterized by the appearance of concentric ring around the tail frequently followed by sloughing all or part of the tail. The feet may also be swollen or reddened. The cause is thought to be environmental condition i.e. R.H <40% or temp. >80o F.

1.12.6.7 Hair Growth Cycle Arrest (?)

Occasionally one may see an entire litter of runted mice about weaning age with complete loss of hair. A small tuft of the hair remain on the base of tail and head or legs. Such mice generally have severe systemic disease ex. M.H.V., and presumably experiencing a temporary arrest of normal hair growth cycle.

1.12.6.8 Infertility

The more common cause of decreased reproductive efficiency can be the result of physiological, neoplastic, infectious or toxicological aberrations. Physiological causes of infertility include senescence, starvation or poorly balanced diets, cystic ovaries, and abortions or irregular estrous cycle induced by inadvertent exposure of wild male mice to established breeding colonies. Neoplastic diseases of the reproductive tract or those that result in debilitation usually coincide with the aging processes or with specific inbred strain characteristics. Primary pathogenic bacteria and viruses responsible for low fecundity have been discussed, but cultural and serological data may not reveal specific pathogens. Enteric bacteria such as E. coli, Proteus spp., and Klebsiella pneumoniae have been isolated from abscessed preputial glands or infected uteri. Contamination of food or water with chemicals such as organophosphates have been incriminated in inducing abortions. Estrogens in feeds have induced scrotal hernias in male mice and poor fertility in female mice. The use of vapona strips in colony rooms to remove mites will cause a cessation of breeding activity until the strips are removed.

1.12.6.9 Neoplasia

1.12.6.9.1 Mammary Tumors (Adenocarcinomas)

Mammary tumors (adenocarcinomas) are fairly common and may be located nearly anywhere in the subcutaneous region due to the extensive distribution of mammary tissue in the mouse. They are virally induced. The virus can be transmitted vertically by passage through the placenta or in the milk. Grossly the tumor is soft, fleshy, and well vascularized. It may contain necrotic tissue and/or blood-filled cysts. Mammary tumors may be surgically removed. Prognosis is poor.

1.12.6.9.2 Lymphosarcomas

Lymphosarcoma is probably the second most common spontaneous neoplastic disease, the incidence of which is dependent on the strain of mouse. C-type viral particles have been observed in murine lymphomas.

1.12.6.9.3 Fibrosarcoma

Fibrosarcoma is the third most common tumor. It is a malignant tumor of fibrous connective tissue - occurs at any age but more common in later stage, common site is the extremities. It is a rounded, lobulated tumor appearing circumscribed or encapsulated with either a hard and/or soft formed collagenous capsule.

1.12.6.10 Dystrophic Calcification (deposition of Ca++ salts in dead or degenerating tissue)

Dystrophic calcification regularly occurs on the epicardium of the heart of inbred strains of DBA/2 and BALB/c mice. Soft tissue mineralization also occurs with lower incidence in other viscera such as the kidney, liver, serosa of the stomach, small and large intestines, and gonads. The mechanism of this disorder is unknown.

1.12.6.11 Retinal Degeneration

This is a common condition in rats, but mice are also affected. It is caused by keeping animals too close to an intense light source. Condition is hereditary in origin.