2.1 Taxonomy:

Order: Rodentia

Suborder: Myomorpha

Family: Muridae

Genus: Rattus

Species: norvegicus (Norwegian rat), or rattus (black or roof rat)

Origin: Old World

Principal Strains: Sprague Dawley Wistar Long Evans Hooded

2.2 Characteristics:

Long hairless tail; well defined behavior, anatomy, physiology and nutritional requirements; easy to handle; small space requirement; few spontaneous diseases; large litters; may bite; have no gallbladder. 

2.3 Biological Data:

Age at puberty:	50-60 days
Minimum Breeding Age:	55-60 days (females weigh 250 gm and males 300 gm)
Breeding Season:	Any time of year
Estrus Cycle:	polyestrus
Duration of estrus cycle:	4-5 days
Duration of estrus:	12 hours
Gestation:	20-22 days
Litter size:	6-12 young (litter size and fertility decreases after 8-10 litters)
Number of litters:	6-10
Ovulation time:	9-10 hours, after onset of estrus
Postpartum return to estrus:	Within 48 hours of parturition. Simultaneous lactation and pregnancy may delay implantation 3-7 days.
Birth weight:	5-6 grams
Weaned:	21 days (40-50 gms)
Weight at maturity:	300 to 400 grams = male 260 to 300 grams = female
Breeding life of female:	l year
Breeding life of male:	l year
Life span:	Excess of 3 years
Mating Colony:	Monogamous system or polygamous system with one male to 2-6 females. Male usually separated from female.
Recommended temperature:	65o-85oF
humidity:	30-70%
light:	12 hours/day
Body temperature:	99.lo or 37.5oC
Mammae:	6 pairs (extend over back and shoulders)
Housing (Minimum):	Weaning to 100 gm - 172 inch. 100-200 gm 232 inch. 201-300 gm - 292 inch. 301-400 gm - 402 inch. 400-500 gm - 602 inch. More than 500 gm - 702 inch.
Cage Height:	7 inches
Diet:	Commercial rodent chow fed ad libitum
Feed Consumption:	5 grams feed per 100 gram body weight (adult) per day
Water Consumption:	10 ml water per 100 gram body weight per day
Blood Sampling:	Nick tail, nick toe, cardiac puncture*, from abdominal aorta*, from jugular vein, orbital sinus* *(Not for use in pet rats)
Anesthetics:	Sodium pentobarbitol (IP): 10-30 mg/kg in young rats 30-50 mg/kg in older rats Ketamine HCl: 10-60 mg/kg produces poor relaxation Ketamine: 60 mg/kg + sodium pentobarbitol (IP): 20 mg/kg - anesthesia will last one hour Innovar-Vet (IM): 0.02 mg/100 gm Ether, methoxyflurane, and halothane on gauze   Note: Rats housed on cedar or pine beddings have reduced barbiturate sleeping time.
Dental formula:	2(I l/l C 0/0 P 0/0 M 3/3, incisors continually erupt)
Uses in Research:	Nutritional studies, dental studies oncology, behavioral research, models to study inherited and induced diseases, model to study pathogenesis and chemotherapy of malaria, drug evaluation studies, behavioral research.
Hemogram: RBC:	7-10 x 106/mm3 (avg. 9.35 xl0 6/mm3) Hct: 49-5ml /100 ml (or 49-54%) Hb: 13.5-16.5 gm/100 ml3 WBC Total: 6-18 x l03 /mm3 (avg. 9 x l03 /mm 3) PMN: 20% Lymph: 78% Mono: 4% Eos: 2%

  

2.4 NUTRITIONAL, REPRODUCTIVE, AND METABOLIC DISEASES OF THE RAT:

Ringtail - unweaned rats housed in low (20% or less) ambient humidity may develop annular constrictions of the tail. Condition may also be caused by temperatures above 85oF or freezing.

Rough hair coat - from malnutrition, febrile disease, old age, ectoparasites

Chromodacryorrhea - "red tears", under stress, harderian glands secrete porphyrin

Infertility - Vitamin E deficiency, Organophosphate poisoning, high temperature and humidity, and infection

Litter desertion, cannibalism or death - excessive noise, deformed young, agalactia

Torticollis - otitis interna, pituitary adenoma; bacterial infections

Malocclusion - incisors mostly involved

Anorexia

Overheating or chilling

Ptyalism - from overheating or malocclusion

Neoplasia - most common tumor is mammary fibroadenoma, leukemia, and pituitary adenomas occur in old rats

Nephrosis

Bite wounds

Dermatitis - bacterial and fungal infection mostly

Starvation

Alopecia - mutual grooming, fungal infection, abrasion on cage or bedding

Adynamic ileus - chloral hydrate toxicity

2.5 BACTERIAL DISEASES OF THE RAT: 

Bacillus piliformis

Tyzzer's Disease 

Bordetella bronchiseptica

Causes pneumonia and upper respiratory disease or rats act as carriers. 

Corynebacterium kutscheri

Rough hair coat, hunched posture, anorexia 

Diplococcus pneumoniae

Acute respiratory infection of young rats 

Mycoplasma pulmonis

Chronic respiratory disease and middle ear disease (labrynthitis) when it extends to the inner ear .

 Pasteurella pneumotropica 

Salmonella

S. typhimurium, S. enteridis - paratyphoid disease 

Streptococcus pneumoniae

Respiratory infection 

Cilia-Associated Respiratory Bacillus

Chronic Respiratory Disease (???)

DERMATOPHYTOSIS: 

Trichophyton mentagrophytes

Causes generalized partial alopecia and slightly hyperemic, scaly skin = ringworm.  

2.6 VIRAL DISEASES OF THE RAT

Sendai virus

Dyspnea and decreased fecundity

Sialodacryoadentitis virus

Affects harderian gland, submaxillary and parotid salivary glands, cervical lymph nodes and lacrimal glands.

Hemorrhagic fever with renal syndrome:

(Syn: Korean hemorrhagic fever, mucoid virus nephropathy): Pathology in rats unknown. Major zoonotic disease, rats act as carriers. Disease in human includes proteinuria, azotemia, petechia, hemoconcentration and renal failure. Mortality in human may occur; but recovered humans are immune to reinfection (see Cox, et al. 1984, p. 111.)

2.7 PARASITES OF THE RAT

Flagellates

• Giardia muris - small intestine
• Hexamita muris - small intestine and cecum
• Trichomonas muris - small intestine, cecum and colon

Sarcodine

• Entamoeba muris - amoeba in the cecum and colon

Sporozoans

• Eimeria miyairii - coccidia in the small intestine 

Cestodiasis:

• Hymenolepis nana - small intestine
• Hymenolepis diminuta - small intestine
• Taenia taeniaformis - (Cysticercus fasciolaris) - larval form in rats and mice

Nematodiasis: 

• Strongyloides ratti - small intestine 
• Gongylonema neoplasticum - stomach

Oxyuridiasis:

• Syphacia muris - pinworm -- in cecum and to lesser extent colon
• Aspicularis tetraptera - pinworm- upper color and to a lesser extent cecum

Acariasis:

• Liponyssus bacoti - most of its life cycle off rat, sucks blood
• Notoedres muris - "itch mite" which invades skin

Pediculosis:

• Polyplax spinulosa - blood sucking lice that transmits the agent of murine hemobartonellosis

2.9 RAT DISEASES 

2.9.1 OBJECTIVES 

• l. Be familiar with the common respiratory pathogens of the rat. Know how these agents may be differentiated from one another (clinical signs, lesions, specific diagnostic tests, etc.), how may be treated, and how they may be controlled.
• 2. Be familiar with the virus that affects the salivary and lacrimal glands of rats. Know clinical signs, lesions, diagnosis, and methods of control.
• 3. Be familiar with Tyzzer's disease in the rat . Know how the disease in rats, as it is clinically described, differs from that in other Laboratory animals.
• 4. Know the clinical signs and methods of diagnosis, treatment, and prevention of ringtail, malocclusion, and retinal degeneration in rats.
• 5. Be familiar with the more common neoplasms of rats.
• 6. Know clinical signs, pathological effects, methods of diagnosis, and treatment of the following parasites: 

  Hymenolepis nana

  Hymenolepis diminuta

  Syphacia muris

  Polyplax spinulosa

  Radfordia ensifera 

2.9.2 BACTERIAL DISEASES 

2.9.2.1 Murine Respiratory Mycoplasmosis (MRM)

Synonyms:

Chronic Respiratory Disease (CRD)

A. Etiology:

2.9.2.1.1 Mycoplasma pulmonis

Microorganism lacking a cell wall.

B. Transmission:

Aerosol, intrauterine (congenital) and direct contact are three known modes of transmission. Intracage NH3 enhances progression of MRM in rats; whereas, sendia virus enhances it in mice.

C. Clinical Signs:

Most infections are subclinical with the organism carried in the upper respiratory tract. The acquisition of primary viral or bacterial respiratory pathogens activates subclinical mycoplasma infections. Early signs of overt disease may include a red (porphyrin) occulonasal discharge, nasal mucus, snuffling sounds, and otitis media. As the organism travels down the respiratory tract, labored breathing, ungroomed hair coat, anorexia, chattering, coughing and hunched posture may be observed. This leads to bronchopulmonary Syndrome. Genital infection is also seen and it leads to infertility, embryonic resorption and small litters.

D. Gross Pathology:

In some cases, the lungs may be grossly normal. A purulent discharge may be found on the nasal mucosa and within the tympanic bullae. Purulent exudate can be found in the trachea and the bronchi. This causes yellow foci in the parenchyma due to bronchiectasis and red to gray areas of consolidation.

E. Diagnosis:

Histopathological examination of the Lungs show peribronchiolar lymphoid hyperlasia. Care should be taken not to confuse the bronchiolar-associated lymphoid tissue (BALT), which is normally present in rat lungs, with a lesion of mycoplasmosis The penetration of the muscular layer of the bronchi by migrating Lymphocytes is considered indicative of MRM. A purulent broncho-pneumonia may also be present. 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 for 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 (l.0 mg/ml water), tetracycline (3-5 mg/ml water), sulfamerazine (0.2% in water or l mg/4 gm food), Chloranphenicol (MychelR mg/kg divided b.i.d.) and Tylosin 10 mg/kg b.i.d. for 5 days have all been reported to reduce mortality. A carrier state will probably remain after treatment.

G. Control:

Since intrauterine infection can occur, infection may persist despite cesarian derivation. Rigid sanitary measures are essential. Atmospheric ammonia (as low as 25 ppm) from urine-soaked bedding can greatly aggravate the condition of the rats and precipitate pneumonia where only rhinitis and conjunctivitis had been present.

H. Importance:

MRM is the single most important disease of rats. Although the disease may be acute, it is usually chronic, resulting in shortened lifespan and experimental results of dubious value.

I. Other Species of Importance:

2.9.2.1.2 Mycoplasma arthritidis

Causes polyarthritis in rats. No infection in mice has been reported.

2.9.2.1.3 Mycoplasma collis

Inhabits conjunctiva and nasopharynx of rats. Significance is unknown. Rats with natural infection developed or had conjunctivitis. 

2.9.2.2 Corynebacteriosis (Pseudotuberculosis)

A. Etiology:

Corynebacterium Kutscheri - a gm (+) short rod containing metachromatic granules. Appear as Chinese letter-like arrangement on gram-stained smears.

B. Transmission:

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

C. Clinical Signs:

Once stressed, the rat may exhibit the typical sick rat syndrome (rough hair coat, hunched posture, anorexia) accompanied with dyspnea and an oculonasal discharge. In rats, arthritis or abscesses in most any organ may occur. The same thing also has been reported in mice.

D. Gross Pathology:

Large, often coalescing, white caseated purulent foci are present in the lungs (hence the name pseudotuberculosis). Unlike the case in the mouse, lesions in organs other than the lungs are rare. In mice multiple white foci of necrosis are seen in liver and kidney.

E. Diagnosis:

Impression smear of lesion with gram stain, observe gram +Chinese letter formation. Culture of pulmonary abscesses provides the definitive diagnosis. Available serological tests include tube agglutination and ELISA.

F. Treatment: None.

G. Control:

Identification of the carrier animals (by cortisone provocation, 10 mg/animal IP, or serological survey) and elimination from the colony. 

2.9.2.3 Salmonellosis:

New CDC classification:

Salmonella enteritidis var. typhimurium - common in laboratory animals and Salmonella enteritidis var. enteritidis - not common in laboratory animals

A. Etiology:

Salmonella typhimurium, Salmonella enteriditis

B. Transmission:

Fecal-oral route. Food, water and bedding may be contaminated by toxin producing enteric bacterium.

C. Clinical Signs:

Disease in susceptible colonies may be manifested only as acute death with moderate morbidity with high mortality. Diarrhea may or may not be present and abortions can occur in pregnant females. Carrier state follows overt disease and may be manifested in breeding colonies as abortion or chronic low fertility. A colony of affected rats may have conjunctivitis.

D. Gross Pathology:

In acute deaths, visceral congestion and petechiation from septicemia may be the only lesions. The spleen may be enlarged 2 to 3 times normal size. In subacute infections, multiple white to yellow foci occur in an enlarged liver. Lesions in the small intestine consist of mucosal congestion and edema with thrombosis of the mesenteric vasculature. Enlarged and prominent Peyer's patches may be seen throughout the ideal serosa.

E. Diagnosis:

The history and gross lesions are suggestive of salmonellosis. Histopathological examination usually confirms gross necropsy lesions. 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 broth, brilliant green and MacConkey's agar with serotyping of the isolate provide the definitive diagnosis.

F. Treatment:

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

G. Control:

Aggressive sanitation procedures should be aimed at preventing contamination of food, bedding, water, or the rats by wild vermin and proper disinfection of cages and watering equipment.

H. Public Health Significance:

Humans ingesting Salmonella typhimurium contaminated food or water experience a transient diarrhea. It is a zoonotic disease.

2.9.2.4 Tyzzer's Diseases

A. Etiology:

Bacillus piliformis - a gm (-) obligate intracellular rod, which forms spores and is motile by peritrichous flagellae. Does not grow on commercial media (see diagnosis, below)

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, or poor housing conditions.

C. Clinical Signs:

Death is often the only indication of infection. Anorexia, hunched posture, and rough hair coat may precede death. Diarrhea has not been reported in the rat.

D. Gross Pathology:

A "fat rat" syndrome with a flaccid segmental dilatation of the intestine (especially of the ileum) has been described. the liver typically has multiple pale foci throughout. Circumscribed, grayish foci may sometimes be observed in the myocardium (not seen in mice). 

E. Diagnosis:

Since the organism cannot be propagated on artificial media, diagnoses are made by demonstration of the bacillus in the hepatocytes bordering necrotic liver foci with silver stains, Giemsa, or PAS. Chick embryo at 9 days old can be used for growth of B. pilliformis.

F. Treatment:

Oxytetracycline at 0.l mg/ml water for 30 days has been reported to abate an epizootic.

G. Control:

Avoidance of stress and strict sanitation help prevent outbreaks. 

2.9.2.5 Pasteurellosis

A. Etiology:

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

B. Transmission:

Aerosol, oral-fecal and contact with infected secretions (including venereal transmission) has been reported. Mice and other laboratory rodents also carry the bacteria.

C. Clinical Signs:

Generally, It is a low grade chronic infection without clinical signs. Primary or secondary disease can affect three body systems, respiratory, reproductive, and skin. Upper respiratory signs are nonspecific such as conjunctivitis, sinusitis, and otitis media. A bronchopneumonia rarely develops. Uterine infection is usually silent; however, decreased reproduction and abortion may occur.

D. Gross Pathology:

Gross lesions are not pathognomonic for the disease and are often intensified by concommittant infections with Sendai virus, mycoplasma, etc. A porphyrin stained oculonasal discharge and focal to patchy consolidation of the lungs may be observed. There may be a purulent metritis; however, in many cases the infected uterus may appear normal. Skin and mammary gland infections resemble typical abscesses.

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.

F. Treatment:

In most colony cases, treatment is unfeasible. Many isolates are resistant to tetracyclines. Ampicillin (5 mg/lb) has been reported to get rid of the carrier states. Chloramphenical (30 mg/kg split b.i.d. for 5 days) has also been used.

G. Control:

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

2.9.2.6 Streptococcosis

A. Etiology:

Streptococcus pneumoniae (Diplococcus pneumoniae - old name is Pneumococcus pneumoniae) It is an encapsulated, gm (+), Lancet-Shaped diplococcus.

B. Transmission:

Direct contact; aerosol. Humans may carry in their throats as normal flora - a 40 to 70% incidence has been reported.

C. Clinical Signs:

Typical "sick rat" signs; serosanguinous to mucopurulent nasal discharge; rhintis, sinusitis, conjunctivitis, otitis media. Younger age groups are particularly affected. Convulsions are also seen.

D. Gross Pathology:

Fibrinopurulent pleuritis and pericarditis; fibrinous lobar pneumonia, consolidation of lung lobes; frothy, serosanguinous fluid in trachea.

E. Diagnosis:

Culture of affected tissue; gross pathology; Gram stain tissue smears to reveal gram positive lancet shaped bacteria in pairs; histopathological examination of lungs (a fibrinopurulent bronchopneumonia); tissue gram stain showing typical organism.

F. Treatment:

Oxytetracyline at 0.l mg/ml in the drinking water for 7 days has controlled epizootics but not eliminated the carrier state. Penicillin may also be tried.

G. Control:

Good husbandry; do not mix rats from different sources; elimination of carriers; reduction of environmental stress.

 

2.9.2.7 Cilia Associated Respiratory (C.A.R.) bacillus

• - Significance is uncertain
• - Occurs in laboratory and wild rodents
• - Filamentous bacterium with slow gliding motility.
• - Causes respiratory infections in rats.
• - Organism grows in embryonated hen's eggs
• - Stains with warthin - Stary Silver Stain
• - ELISA Test is presently being tested and holds promise

  Reference: Infect. Immun. 47 (2):472-479, Feb. 1985.

 

2.9.2.8 Streptobacillus moniliformis

• - Gram (-) rod that occurs singly or in long filamentous chains.
• - Occurs in rats, most commonly isolated from nasopharynx, middle ear, respiratory tract and subcutaneous abscesses or may have no signs
• - Transmission is by bite wounds, aerosols and fomites
• - May occur in mice housed near infected rats. Signs in mice include conjunctivitis, photophobia, Cyanosis, diarrhea, anemia, hemoglobinuria, emaciation and high mortality. In chronic cases, deformity or the sloughing of limbs occurs or sloughing of tails results.
• - In man, cases resulting from rat bites have been referred to as "rat-bite fever" and milk borne epidemics as "Haverhill fever"

Diagnosis:

Differential diagnosis should include mouse pox, Corynebacterium Kutscheri and salmonella infection since this also causes septicemia similar to what occurs in Salmonellosis.

Control:

Avoid housing mice and rats in the same room. In rats use only cesarian derived stock and maintain in a barrier facility.

(See the table on the following page for comparison with Spirillum minus) 

Staphylococcus aureus:

• - Ulcerative dermatitis in rats - common
• - Traumatic pododermatitis in rats - exercise on circular activity wheels causes abrasions and lacerations with secondary staphylococcal pododermatitis. 

 

2.9.2.9 A COMPARATIVE TABLE OF STREPTOBACILLUS MONILIFORMIS AND SPIRILLUM MINUS

(Both cause Rat Bite Fever in Humans) 

Streptobacillus moniliformis

Spirillum minus

Gram Stain	Gram negative	Gram negative
Incubation Period	2-10 days	2-3 weeks or more
Location	Found in nasopharynx of of normal, healthy .Sometimes causes conjunc- tivitis in rats. -Organism is shed in urine.	Found in blood apparentlyhealthy rats rats.
Disease	Bite lesions heal promptly. and indurate at the site of bite. Regional lymphadenitis.	Bite lesions heal Regional lympha- denitis Fever, chills, myalgia, Fever, chills, sore throat, arthritis, myalagia, and a morbiliform pink and a purple to petechial rash. red- brown macular rash
Complications	Abscesses, anemia,	Endocarditis mastoiditis, endocardi- tis, pericarditis
Diagnosis	Culture of patient's Demonstration blood of spirilla via lesions using enriched microscopic media. Culture of local dark-field exam of blood or peritoneal fluid of a mouse or guinea pig, inoculated 2 weeks prior, with blood or wound fluid from patient.   Animal inoculation can Serological also be used. Mice tests can be are used; guinea pigs done but are are unsatisfactory. usually ineffective.	-
Treatment	Penicillin and other antibiotic are effective.	Penicillin and other anti- effective. biotics are effective.
Zoonotic disease ?	Yes	Yes

Source: ACLAM Rat Book, Volume 1, p. 403. 

 

2.9.3 VIRAL DISEASES 

2.9.3.1 Sendai Virus Infection

A. Etiology:

RNA virus. Family - Paramyxoviridae; Genus - Paramyxovirus; Species - Parainfluenza I (Sendai).

B. Transmission:

Aerosol and direct contact. Infections are usually enzootic in a colony. 

C. Clinical Signs:

May see sick rats with dyspnea or decreased fecundity. Simple Sendai infections rarely cause death; however, the virus is immunosuppressive and concomitant respiratory infections with the other respiratory pathogens of rats are frequent; e.g., Mycoplasma pulmonis.

D. Gross Pathology:

The lungs of affected rats may be mottled. Red and tan foci in the parenchyma and exudate in the major airways may be seen. In uncomplicated Sendai infections, only the lungs are affected.

E. Diagnosis:

Histological examinations reveal characteristic interstitial pneumonia with perivasculitis, hyperplasia of alveolar macrophages, and bronchiolar exudate. Complement fixation, HAI, and ELISA reveal antibody titers.

F. Treatment:

The disease is difficult to treat. A vaccine is commercially available and is showing relative success. It is available commercially.

G. Control:

Cessation of all breeding activity in the colony for 60 days (why? - because infection has run its course and the virus has been eliminated naturally) and concomitant removal of all suckling and weanling animals will eliminate the infection. 

2.9.3.2 Sialodacryoadenitis Virus Infection

A. Etiology:

RNA virus. Family - Coronaviridae; Genus - Coronavirus. Significance - high.

B. Transmission:

The virus is highly contagious and is spread by aerosol, direct contact, and fomites.

NOTE: Virus is present in tissues of infected rats only for 7 (seven) days and there is no carrier state.

C. Clinical Signs:

The disease is not fatal and may be subclinical. The tats may exhibit a porphyrin oculonasal discharge. The submaxillary salivary gland may be palpably enlarged due to sialoadenitis. Dacryoadenitis may cause exophthalmus which can lead to keratitis and corneal ulcers.

D. Gross Pathology:

Enlarged submaxillary and parotid salivary glands; edematous cervical lymph nodes; swollen lacrimal glands; yellow-gray foci in Harderian gland (brown-red mottling of the Harderian glands is normal and is due to porphyrin). Thymus and lungs are also affected.

E. Diagnosis:

Histopathological examination of submaxillary salivary gland reveals degenerative changes including acinar and ductal epithelial necrosis, interstitial edema, squamous metaplasia of ductular epithelium followed by proliferation of hyperchromatic acinar cells. Chronic lesions include replacement of acini with fibrous connective tissue and an infiltration of lymphocytes. Similar lesions are present in the lacrimal and Harderian glands. The sublingual salivary gland (mucus secreting) is usually not affected. Eye lesions may include interstitial keratitis, corneal ulceration and conjunctivitis.

Other diagnostic techniques include CF, immuno-fluorescence and clinical signs.

F. Treatment: None.

G. Control:

Good husbandry. No carrier state exists and recovered rats are free of virus and are immune. No effective vaccines are available. The immune status of the colony and of any new rats to be introduced should be monitored serologically.

H. Importance:

Interferes with studies of respiratory system, salivary glands and eyes. Infected rats are at a greater risk for inhalation anesthesia.

 

2.9.3.3 Rat corona virus (R.C.V):

No natural infection. 

2.9.3.4 Pox Virus infection rats:

Two infection in U.S.S.R. in 1973 and 1974. Significance unknown.

2.9.3.5 M.H.G. Virus:

McConnel, Huxsoll, Garner et al. (1965). Probably a picorna virus. Significance unknown. 

Reference: Proc. Soc. Exp. Biol. Med. 115:362-367, 1965.

 

2.9.3.6 Rat Virus, Toolan H-2 Virus and Minute Virus of Mice:

DNA Virus; Family - Parvoviridae; Genus- Parvovirus. Rat virus Synonym - Kilham Rat Virus

Only Rat Virus causes natural infection; other two only experimental infection. Natural infection includes fetal resorption in pregnant rats and small litters. Pups are runted, atactic and jaundiced. HAI is used for diagnosis.

Clinical Signs:

Circling, incoordination, tremors, torticollis and high mortality in adult rats. 

2.9.4 PARASITIC DISEASE 

2.9.4.1 Protozoal Diseases

2.9.4.1.1Spironucleus muris (Hexamita muris)

A flagellated protozoa that dwells in the crypts of Lieberkuhn of the small intestine and in the glands of the gastric pyloris.

1. Transmission:

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

2. Clinical Signs:

Rats are clinically unaffected.

3. Diagnosis:

Direct smears of the contents reveal fast darting protozoa. Histological examination of the duodenum will reveal the protozoa in the crypts and along the surface of the villous epithelium. Cysts can be detected in the feces.

4. Treatment:

Dimetridazole (l% solution or l gm/l drinking water) has been reported to decrease the parasite load.

2.9.4.1.2 Giardia muris

A common flagellate protozoan in anterior small intestine. Transmission is by ingestion of cysts. The protozoan is of low pathogenicity, but can cause digestive disturbances, malnutrition, or even ulcers when present in large numbers. Diagnosis is by recognition of the pear-shaped, bilaterally symmetrical organisms on histopathological examination or by a direct smear of intestinal contents. Control depends on proper sanitation.

2.9.4.1.3 Trichosomoides crassicaudata

Bladder thread worm of rats. It is a round worm that occurs in the urinary bladder of rats. Significance is low.

2.9.4.1.4 Pneumocystis carinii

It is a unicellular protozoan or fungal extracellular parasite. It is usually a latent or subclinical pulmonary disease in rodents. Causes pneumonitis. It is a common organism found in humans showing the signs of Acquired Immuno-deficiency Syndrome (A.I.D.S.).

Treatment:

Sulfadiazine plus pyrinrethamine or stilbamine. 

2.9.4.2 Cestodes

2.9.4.2.1 Hymenolepis spp.

1. Etiology:

Hymenolepis nana (dwarf tapeworm) and Hymenolepia diminuta.

2. Transmission:

Hymenolepis nana and Hymenolepis diminuta can be transmitted by an indirect mode with cockroaches, fleas or beetles 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 14-15 days).

3.Clinical Signs:

Usually there are no external signs of infection. However, catarrhal enteritis, diarrhea, emaciation and chronic weight loss may occur with heavy infestations.

4.Gross Pathology:

Hymenolepis nana adults range from 25-40 mm long and less than l mm wide and have an armed rostellum. Hymenolepis diminuta adults range from 20-60 mm in length and 3-4 mm wide without hooks on scolex. Often the tapeworms migrate up the pancreatic and biliary ducts.

5.Diagnosis:

Visualization of ova on fecal floatation; visualization of adults on histopathological section of the intestine.

6.Treatment:

Niclosamide (YomesanR) at 10 mg/100 gm body weight given in 2 treatments at 7 day intervals.

7.Control:

Insects should be eliminated and infected animals treated.

8.Public Health Significance:

Humans are susceptible to Hymenolepis nana infections; since autoinfection can occur, a heavy parasite load may quickly develop.

2.9.4.2.2 Taenia Taeniaformis

Rats serve as intermediate hosts for the cat tapeworm Taenia Taeniaformis. The cysticercoid cyst (Cysticercus fasciolaris) embeds in the liver and may cause a palpably enlarged liver if cysts are numerous. Infection occurs when rats ingest ova in cat feces; fecal contamination of rat food or bedding can occur. No treatment is necessary but prevention of feline fecal contamination of rat food or bedding.

 

2.9.4.3 Oxyurids 

2.9.4.3.1 Syphacia muris (rat pinworm)

1.Transmission:

Syphacia muris deposits eggs in the perianal region. 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 lead to catarrhal enteritis, rectal prolapse, or perianal irritation.

3.Gross Pathology:

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

4.Diagnosis:

Direct exam of cecal contents, fecal flotation and tape test of the perianal region will identify adults and eggs, respectively.

5.Treatment:

If treatment is desired, piperazine (4-7 mg/ml water) for 3-l0 days is effective. Karo syrup can be added to the solution if the rats refuse to drink it.

6.Control:

Prevention and control of infection are often difficult. Rigid sanitary procedures, use of filter hoods to prevent aerosol transmission, and regular ova examinations with treatment may control the parasitism.

2.9.4.3.2 Syphacia obvelata and Aspicularis tetraptera

These mouse pinworms may infect rats. The comments made about Syphacia muris also apply to Syphacia obvelate, with which it is frequently confused. Aspicularis tetraptera inhabits the colon and deposits its eggs in the feces; thus, it cannot be diagnosed by use of the anal tape test.

2.9.4.4 Lice

2.9.4.4.1 Polyplax spinulosa (Spined blood sucking Rat Louse)

A.Etiology:

Polyplax spinulosa - Sucking spined louse of rats

B.Transmission:

Direct contact with infected host or bedding.

C.Clinical Signs:

Scratching, irritation, restlessness and debilitation.

D.Pathological Effects:

The louse is a blood sucker and causes anemia. It is the vector of Hemobartonella muris and other blood borne pathogens.

E.Diagnosis:

Identification of adult lice, nymphs, or eggs on the fur.

F.Treatment:

Vapona strips (No PestR, Dichlorvos) placed above cages for 24 hour intervals every 7 days. Adults and weanlings can be dusted with silica dusts, pryethrin dusts, or can be dipped in a 2% malathion solution. Contaminated rooms can be fumigated with formaldehyde.

G.Control:

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

2.9.4.5 .Rat Mites

A.Etiology:

2.9.4.5.1 Radfordia ensifera

Radfordia ensifera is a rat fur mite that is closely related to Myobia musculi and Radfordia affinis of mice.

B.Diagnosis:

Visualization of mites on hairs with the aid of a dissecting microscope - as is done in diagnosing the mouse mites.

C.Life Cycle, Transmission, Pathological Effects, Treat-ments, and Control: Unknown, but presumably similar to those of Myobia musculi of mice.

2.9.4.5.2 Notoedres muris - Rat mange mite (rare)

2.9.4.5.3 Liponyssus bacoti

The tropical rat mite - sucks blood and may cause anemia if heavy infestation is present.

2.9.5 NEOPLASIA

2.9.5.1 Mammary Fibroadenoma

This is most common tumor of rats. Because of the extensive mammary tissue present in rats, tumors may be found practically anywhere - behind the shoulder blades, at the base of the tail, etc. Tumors may occur in males as well as in females. The tumors which appear as subcutaneous lumps may be quite extensive. Ulceration and subsequent dermatitis occur frequently. Tumors are usually encapsulated and benign. With surgical removal, the prognosis is good.

2.9.5.2 Pituitary Chromophobe Adenoma

This is an extremely common tumor of rats, although incidence varies with strain. Grossly, tumors are soft with an irregular surface and may have prominent hemorrhagic areas. They are generally well circumscribed and compress adjacent brain tissue and occasionally cause hydrocephalus. The tumor tissue appears soft grayish white and is susceptible to hemorrhage, degeneration and cyst formation.

2.9.5.3 Mononuclear Cell Leukemia of Rats

This neoplastic condition has been described in Fischer 344 rats (25%), Wistar-Furth rats (17%), Wistar rats (2%) and Sprague-Dawley rats. Affected rats are depressed, pale, icteric and have palpably enlarged spleens. Also seen are enlarged mesenteric lymph nodes and mottled livers. Spleens have diffuse leukemic cell infiltration of red pulp and follicle depletion. Liver lesions are characterized by centrilobular degeneration and necrosis with leukemic cells in sinusoids and often periportally. Erythrophagocytosis is common in spleen and liver. This disease starts in the spleen and bone marrow involvement occurs later in the disease. The lungs are infiltrated and have multifocal nodules of tumor cells within alveolar walls with hemorrhage and necrosis. Tumor cells may be free in the alveolar spaces. Sometimes diffuse alveolar wall infiltration is seen. Small foci of tumor cells are seen in the adrenal glands. Massive lymph node infiltration with effacement is common.

Interstitial-Cell Tumor:

Common in rats, but rare with a spontaneous incidence in mice. At necropsy, tumors appear as focal, unilobulated and/or multilobulated soft tan or yellow masses embedded in the testicular parenchyma. They may be bilateral. Microscopically, there is usually a uniform population of proliferating Leydig cells with abundant eosinophilic cytoplasm. Small hyperchromatic reserve cells can be present. They can be very vascular and/or hemorrhagic. They may become large but most appear benign.

Auditory Sebaceous Adenocarcinoma:

This tumor is often called as the "Zymbal Gland Tumor." They are modified sebaceous glands located near the base of ear in rats. Other rodents or rabbits do not have this gland. Grossly, rats may have unilateral (or bilateral), ulcerated, firm swelling(s) on right or left or both sides of the face at the angle of the mandible near the ear. The rats may have porphyrin stain around both eyes; otherwise, they appear normal. Microscopically, the ulcerative lesions of the face consist of irregular lobules of cells separated by thick fibrous septa. The cells are basophilic, oval to polygonal in shape and are arranged either as ducts, cysts with papillary projections or acini. The cells have large vesicular nuclei and nucleoli with surrounding halos. A high mitotic index may be seen.

 

2.9.6 MISCELLANEOUS CONDITIONS

2.9.6.1 Malocclusion (Mandibular prognathism):

A condition caused by overgrown incisors which may be due to trauma, bacterial infection or genetic factors. Hypersalivation may be observed. Treatment consists of clipping overgrown teeth with nail clippers.

2.9.6.2 Ringtail:

NOTE: Rat's tail serves as a temperature control device.

A.Etiology:

Insufficient environmental humidity (<20%),and artificially increased temperature,of over 80o F or freezing. Freezing may not be possible in the animal room.

B.Clinical Signs:

Annular constriction may be observed in weanling rats. Tails may slough. Ringtail is commonly seen from November to May when room air is dried due to heating systems.

C.Diagnosis:

Clinical signs and history of low environmental humidity and temperature of about 80o F or freezing.

D.Treatment:

None for affected rats. Tail stumps usually heal without complication.

E.Prevention:

Provide sufficient environmental humidity and maintain proper temperature control.

 

2.9.6.3 Chronic Progressive Nephropathy (CPN):

This condition is also referred to as Chronic Rat Nephropathy or Old Rat Nephropathy. It has been observed in Sprague-Dawley, Fischer 344, Wistar and several other rat strains. The cause is unknown and both tubular and glomerular lesions are seen. Males have a higher incidence than females, but in aged females, the incidence approaches that of males. Severe cases are rarely seen in rats less than one year of age. In rats approaching three years of age, the incidence approaches 75%. Diets high in protein seem to accelerate the development of lesions. Affected kidneys are enlarged and tan in color. Cysts may be present. Microscopically, globular cysts filled with protein in hyalin casts and common tubular epithelial cells are flattened or show hyperplasia. The tubular basement membranes are thickened. Glomerular lesions range from atrophic tufts with thickened basement membranes to epithelial proliferation. Sometimes glomeruli are sclerotic. Interstitial fibrosis is seen late in the disease along with mineralization.

2.9.6.4 Polyarteritis/Periarteritis Nodosa:

Common in old rats and less so in mice. Usually involves small muscular arteries and arterioles in a variety of tissues, including pancreatic, mesenteric, spermatic, hepatic and ovarian vessels. Can be focal or systemic. Pathogenesis can vary, although hypertension and autoimmune reactions have been incriminated. Microscopically, fibrinoid necrosis of the vascular wall, mixed inflammatory cells infiltrating all tunics, fibrosis and intimal proliferation may be seen.

It has been reported that the frequency of breeding during the first 12 months of life influences the age of occurrence of polyarteritis nodosa in rats.

2.9.6.5 Retinal Degeneration:

NOTE: Rats have poor eyesight and depend on facial vibrissae and olfaction for sensory input, a blinded rat may appear, in fact, essentially normal.

This is a common condition of rats housed in a laboratory situation caused by placing animals too near to an intense light source. The condition is hereditary in origin.

2.9.6.6 Gastric Ulcers:

Occurs primarily in the nonglandular portion of the stomach of rats and to a lesser extent in mice. These are occasional findings and very little is known about them.

2.9.7 REFERENCES 1.Harkness, J.E. and Wagner, J.E. The Biology and Medicine of Rabbits and Rodents. Lea and Febiger. 2.Farris, E.J. and Griffith, J.W., Ed.: The rat in Laboratory Investigation. Hafner Publishing Co., Inc., 1949; 1969. 3.Barnett, S.A. 4: The Rat: A study in Behavior. University of Chicago Press, 1975. 4.Breene, E.C.: Anatomy of the Rat. Hafner Publishing Co., Inc. 5.Baker, H.J., Lindsey, J.R., and Weisbroth, S.H., Eds.: The laboratory Rat, Vol. l and 2. Academic Press, Inc., 1979 and 1980. 6.Fox, J.G., et al. Laboratory Animal Medicine. Chapter 4. Academic Press, Inc., 1984.