HAMSTERS BIOLOGY, CARE, DISEASES & MODELS I. INTRODUCTION/HISTORY A. Approximately 1,000,000 hamsters are used in research annually in the united states. Of these, 90% are Syrian (Golden), Mesocrictus auratus, and the remainder are primarily the Chinese(striped back), Cricetus griseus; the Armenian(gray), Cricetulus migratorius; and the European, Cricetus cricetus. By 1971, the hamster had become the third most commonly used laboratory animal in the United States, exceeded only by mice and rats. B. Syrian hamsters, utilized as laboratory animals, originated from one litter captured in Syria in 1930. Only three menbers of this litter were retained in captivity, and it is the progeny of these that were first imported to the United States in 1938. The four main reasons given for selection of the Syrian Hamster for research are (1) availability and ease of reproduction,(2) relative freedom from spontaneous diseases coupled with susceptibility to many introduced pathogenic agents, (3) anatomical and physiological features with unique potential for study, and (4) rapid development with short life cycles. C. The Chinese hamster was first used as a laboratory animal in 1949. Since that time it has been used in several aspects of infectious disease,radiobiological,endocrine, carcinogenic, and mutagenic research. Since the Chinese hamster has the lowest chromosome number of any other placental nurtured lab animal it is useful for cytogenesis research. D. The European hamster developed some laboratory importance when several wild animals caught in a West German industrial area were found to have had bronchogenic squamous cell carcinoma. This hamster has since been found to be susceptible to N-diethylnitrosamine with the resultant development of respiratory tumors. It was concluded that the European hamster is a more suitable model than the Syrian hamster for highly concentrated and prolonged smoke inhalation studies. Also the Europeon hamster is much larger than other hamster species(300-400 gm). E. The Armenian hamster was first introduced as a laboratory animal in 1963. It was selected because of its susceptibility to mutagenic and carcinogenic agents and for studying meiosis. Their diploid chromosome number is 22. II. SYRIAN HAMSTERS A. ORIGIN- The Syrian, hamster is native to the arid, temperate regions of Southeast Europe and Asia Minor. In their natural environment, hamsters live in deep tunnels that ensure a cooler temperature and higher humidity than the general desert environment. B. GENETICS/ANATOMY 1. Taxonomy ORDER: Rodentia FAMILY: Cricetidae GENUS: Mesocricetus SPECIE: auratus 2. Common names: Golden or Syrian hamster,Symbol(SYR) 3. Strains a. Inbred Strain (i.e.,20 or more successive generations of brother x sister matings) Nomenclature of more common types (All developed by Billingham and Silvers at Univ Pa) (1) MHA/SsLak -White--pink eyes;Mill Hill Albino- susceptible to dental caries (2) LSH/SsLak -Brown & white; London School of Hygiene (3) CB/SsLak -Brown & white; Chester Beatty Instutite (4) PD4/Lak -White--pink eyes; (5) LHC/Lak -Cream; Lakeview Hamster Colony b. Outbred Strain Nomenclature (1) Lak:LVG(SYR) -Golden Syrian 4. Genotype- Diploid (2N) chromosome number: 44 5. Phenotypic Characteristics- The adult Syrian hamster is larger than a mouse, usually growing to 6 to 8 inches in length and weighing from 110 to 140 gm. It virtually tailless, and has smooth, short hair. Normal coloration is reddish-gold, with grayish-white ventral portion, however, color can range from albino to dark brown (Other pertinent anatomical features as follows) a. Dentition: (1) Dental formula 1 0 0 3 I- C- PM- M- = 16 1 0 0 3 (2) Incissors (a) Erupted at birth (b) Grow continuously (3) Molars (a) Erupted at birth (b) Cuspidate and do not continue to grow (4) Dental caries is easily induced by altering diet b. Cheek pouches- Evaginations of the lateral buccal wall are devoid of glands and lymphatic drainage. These sites are priviledged for foreign tissue transplant due to this lack of lymph drainage. c. Stomach- Two compartments (a) Non-glandular-similar to ruminants -cardia region (b) Glandulary -acid -pyloric region (c) The two compartments are joined by a narrow passageway with the esophagus entering just proximal to the dividing stricture. d. Sebaceous scent glands (a) costovertebral area (b) larger in male than female (c) function controled by androgens (d) thought to serve as olfactory ID marker e. Pulmonary system (a) Limited numbers of gland in upper airways (b) Left lung- single lobe (c) Right lung-3 lobes(apical,middle,caudal) f. Kidney- The renal papilla extends out into the ureter making it possible to collect urine from tubules in a living hamster. g. Mammary Gland- 14-22 mammae. h. External Genitalia/Sexing (a) Males-greater urogenital distance and only one urogenital opening (b) Females- Separate vaginal,urinary,and anal openings C. PHYSIOLOGY 1. Neonatal Development a. Teeth present at birth,eyes & ears closed, and pups are hairless. b. Ears open at 4-5 days c. Eyes open at 15 days d. Eat solid food at 7-10 days e. Weaned at 21-28 days 2. Normative Data PARAMETER VALUE Adult weight Male 85-140 gm Female 95-120 gm Life span Average 2 years maximum expected 3 years Chromosome number (diploid) 44 Water consumption 30 ml/day Food consumption 10-15 gm/day (adult) Body temperature 36.2-37.5 C (rectal) Heart rate 280-412/min Respiratory frequency 74(33-127) HEMOTOLOGY RBC 7,500,000/mm WBC 7,600/mm Segmented Neutrophils 21.9% Non-segmented Neutrophils 8.0% Lymphocytes 73.5% Monocyte 2.5% Eosinophils 1.1% Basophils 1.1% 3.Reproduction and mating PARAMETERS VALUE Puberty Male 6-8 weeks (90 gm) Female 6-8 weeks (90-100gm) Estrous cycle (1) 4 days Estrus (2) 6-10 hours(night) Gestation (3) 15-18 days Litter size 4-12 pups Birth weight 2-3 gm Weaning (4) 21 days(35-40gm) Optimum breeding life 14 months FOOTNOTES (1) Stage of cycle can be determined by the tenacity and opacity of vaginal discharges-- The discharge is thick and opaque at the time of and after ovulation. (2) Heat generally begins approximately 1-2 hours after dusk on the third day of the estrous cycle and ovulation is completed 6-10 hours after onset of psychic estrus. The female should be placed in the cage with the male at the begining of the dark cycle. If the female is receptive she will quickly assume a lordotic position with hindlegs spread and tail erect. If copulation does not occur within 5 minutes or if the female becomes aggressive, she is removed. If copulation occurs, the pair can be left together until the following light cycle. (3) A copulation plug will be visible for a few hours after copulation. Colony raised females can be returned to the colony until day 14 of gestation if they don't fight. Pregnant animals should be separated and undisturbed for at least 2 days prior to and 7 day after parturition to avoid litter cannibolism. (4) Estrous cycle will not resume for the mother until a few days after her young are weaned. Young from different litters can usually be housed together until 50 days of age. 4. Behavior a. Docile unless surprised or awaken. b. Nocturnal o c. Hibernate when temperature drops below 5 C, however, animal is responsive to external stimuli. d. Curious by nature D. COLONY CARE & HUSBANDRY 1. Housing a. Caging (1) Plastic shoebox solid bottoms/latchable lid to prevent excape. (2) Space requirements (a) Hamster < 60gm - 10sq.in. (b) Hamster > 60gm - 11/20 sq.in. (c) Female with litter - 150 sq.in. b. Bedding (1) Routine types include: hardwood chips, sawdust, shavings, corn cobs, and beet pulp. (2) Pregnant animals will use soft paper for nest building. (3) Bedding should be replaced 1 or 2 times weekly and can be left as long as 2 weeks when is is desirable to leave a litter undisturbed. c. Temperature/Relative Humidity (1) Adults should be maintained at approximately 65 to 70 degrees F with 40-60% relative humidity. (2) Breeding rooms should be kept slightly warmer (71-75 degrees F). (3) Hamsters are more adaptable to cold extremes than to warm extremes. d. Photoperiod: 12-14 hour light period daily with 14 hours required for breeding colonies. 2. Feeding a. Nutritional requirements: Since the hamster's first stage of digestion is a fermentation process their nutrient utilization is slightly different than that of other rodents. Often times rat feed is used as a basic diet and is then supplemented with rabbit chow or other similar diets. (1) Soybean meal provides a better protein supplement than fishmeal at about 16% of the ration. Protein levels of 18-24% promote more rapid growth, but at the cost of higher incidences of nephritis. (2) More complex carbohydrates,such as, corn starch are more highly tolerated energy sources. 30-40% corn starch in the ration is ideal (3) Compared to the rat, the hamster has a higher requirement for zinc, copper, and potassium. b. Feed delivery- If food hoppers are used, the feed pellets must be able to fall through the slots to the floor of the cage. This is required because the hamster's muzzle is so broad as they would be forced to chew food from both sides of the metal strips of the feeder resulting in broken teeth and starvation. c. Water- A continuous supply of fresh clean water is required. Water delivered via Stainless steel siper tubes is most desirable. 3. Handling a. Physical restraint- Insure that the hamster is aware of your presence and is not asleep. (1) Container or cupped palms are often adequate for transfer or weighing. (2) One-hand hold (thumb and 3rd finger around the thorax stablizing the hindquarters with the 1st & 2nd fingers.) b. Chemical restraint/preanesthesia/anesthesia AGENT DOSAGE Ketamine HCL 40-150mg/kg IM 100-200mg/kg IP Xylazine(with ketamine) 10mg/kg IM Improves degree of relaxation Pentobarbital(10mg/ml) 50-90mg/kg IP Pentobarbital(60mg/ml) 90mg/kg IP 30mg/kg IV Thiopental 20mg/kg IV Morphine up to 150mg/kg IM;IP;SC analgesia w/o narcosis Inhalant anesthetics cone;chamber;mask Atropine sulfate 0.2-0.5mg/kg SC c. IV injection site: saphenous vein d. Common bleeding sites: (1) Cardiac puncture (requires anesthesia 2 ml/100gm animal safely) (2) Tail clip (no anesthesia,small quantities) (3) Orbital sinus (requires anesthesia,small quantities) e. Euthanasia (1) Physical methods (a) Cervical dislocation (b) Decapitation (2) Parenteral methods (a) Pentobarbital 135-150mg/kg IV minimum (b) T-61 : not to be used when histo- pathology is anticipated. (3) Inhalant methods (a) Carbon dioxide (b) Halothane (c) Methoxyflurane (d) Ether(explosive) E. SPONTANEOUS DISEASES 1. Hamsters are generally very resistant to diseases and have few health care problems. This, coupled with the fact that diseases can be readily induced, make the hamster ideal as a model for many human diseases. Some disease conditions have been propagated by inbreeding to maintain specific models for human disease which are not common for the species as a whole. 2. Common diseases listed in decending order of occurrance (below) a. Enteritis b. Pneumonia c. Neoplasia d. Amyloidosis (old animals) e. Polycystic disease 3. Enteritis is the most common type of spontaneous hamster disease. The condition may occur due to a broad number of factors from infectious agents to management practices. a. Common names- Wet tail, proliferative ileitis, regional enteritis, and ileal hyperplasia. b. Agents routinely associated with disease. (1) Clostridium difficile is often isolated subsequent to enteric disease associated with antibiotic therapy(i.e. clindamycin ampicillin, lincomycin) which could indicate that this bacterium may play some role in the pathogenisis. (2) Campylobacter Fetus ssp jejuni has been incriminated of late as having a contributing role in the clinical symptoms of enteric disease. Although it is cultured on occassion from clinically normal animals it was reported by Lentsch in almost 100% of the hamsters with symptoms of proliferative ileopathy. c. Predisposing factors (1) Young age. (2) Stress (shipping overcrowding lack of fresh water.) (3) Poor diet. (4) Antibiotic therapy. d. Clinical signs (1) Acute - lethargy, anorexia, ruffled hair diarrhea, dehydration, and death within 48 hours. Intussuceptions may occur. (2) Subacute-diarrhea, retarded growth and eventual death. (3) Chronic-palpable abdominal masses with emaciation or even normal appearance with occassional deaths. e. Histopathology - Hyperplasia of the ileal absorptive epithelium is the primary lesion. f. Treatment - Erythromycin 20mg/kg is most desirable. g. Differential diagnosis. (1) Salmonella spp.- rare spontaneous disease of hamster; Dx culture. (2) Tyzers (a) Clinical signs may include all those listed in regards to proliferative ileitis or animals may just be found dead. (b) Etiology - Bacillus piliformis. (c) Transmission fecal - oral. (d) Pathology - focal necrosis of viseral organs. (e) Diagnosis - tissue smears (silver, PAS or Giemsa stains.) 4 Pneumonias a. Clinical signs - depression, anorexia, nasal and ocular discharges, respiratory distress and chattering. b. Common eitiologies. (1) Pasteurella pneumotropica. (2) Streptococcus spp. (3) Streptococcus pneumoniae. c. Control/Treatment - eleminate stress, depopulate or treat with an effective antibiotic which does not cause fatal enterocolitis. 5. Neoplasia. a. Malignant tumors in (decreasing order of ocurrance. (1) Lymphosarcoma. (a) Horizontally transmitted - no type C or retrovirus identified. (b) Epidemic outbreaks in various breeding colonies have reach 50 -90% mortality. (c) Clinical signs - solid tumors enteritis, pyelonephritis, warts, poor breeding efficiency and intussusceptions. (2) Reticulum cell sarcoma - lymphnodes. (3) Carcinoma - intestines and adrenals. b. Benign tumors (most common). (1) Gastro - intestinal polyps. (2) Adenomas of adrenal cortex. 6. Amyloidosis - principle cause of death in aged hamsters. The incidence can reach or exceed 85% in hamsters over 18 months of age: The kidney is the most likely site of deposition, however, other organs are often involved. The disease compares with the nephotic syndrome described in humans. 7. Polycystic Disease - cyst occur in a high incidence in hamsters over 1 year of age with the site most frequently in the liver. The lesions generally are of no clinical significants and are thought to be due to developmental defects of ductal structures. 8. Spontaneous viral diseases a. Clinical symptoms secondary to common rodent virus (i.e. Sendae,LCM) are rare,however, sero-conversion is common. b. Even though little disease is noted in the hamster lymphocytic choriomeningitis is important because of it's zoonotic implications in humans. 9. Spontaneous parasitic diseases a. Internal (1) Protozoan- Several have been identified but they have little clinical significants. (2) Nematodes Syphacia obvelata(mouse pin-worm) Syphacia muris (rat pin-worm) (3)Helminth (a) Hymenolopsis nana (zoonotic) (b) Hymenolopsis diminuta (c) Can cause obstruction and enteritis (4) Dx- Fecal exam b. External (1) Ornithonyssus bacotis(tropical rat mite) (2) Notoedres spp.(ear mite) (3) Demodex criceti D. aurata-more pathogenic (4) Dx-Skin scraping III. CHINESE HAMSTER A. Native to the Eastern shore of China near the Caspian Sea. They were first successfully bred in 1958, after illumination schedules were reversed. B. Taxonomy ORDER: Rodentia FAMILY: Cricetidae GENUS: Cricetus SPECIE: griseus C. Physiology 1. Mayor differences from Syrian hamsters PARAMETER VALUE Chromosome(2N) 22 Adult Weight 39-46 gm Body Length 4 inches Water Intake 11-13 ml/100gm 2. Reproductive physiology PARAMETER VALUE _______________________________________________________ Incisors Erupted at birth Eyes & ears open 10-14 days Weaned 21-25 days Sexually mature 8-12 weeks Estrous cycle Polyestrus Estrous cycle duration 4 days Estrus 6-8 hours Ovulation time Just before estrus Copulation 2-4 hours after start of dark period Implantation 5-6 days Gestation 20.5 days Average litter size 4-5 Mammae numbers 8 Postpartum estrus 4 days _______________________________________________________ 2. Hemogram similar to Syrian hamster D. Diseases 1. Very few spontaneous infectious diseases reported. 2. Metabolic a. Diabetes mellitus (1) insulin dependent (2) similar to human (3) clinical signs-polydypsia,polyuria, dehydration, blindness and death especially after stress (4) recessive factor-propogated by inbreeding 3. Neoplasia-low incidence 4. Miscellaneous a. Periodontitis-Epecially in those with diabetes which resembles the same condition in humans with diabetes. b. Nephrosclerosis c. Spondylosis- Higher incidence in hamsters with diabetes. IV. EXPERIMENTAL MODELS/USES A. Spontaneous Models of Human Disease 1. Diabetes mellitus in the Chinese hamster was recognized in 1957. The disease is associated with a decrease of the pancreatic B cells. It is insulin dependent, juvinile onset,and hypoinsulinemic similar to the juvinile type in man. 2. Syrian hamster dystrophy a. strains: BIO 1.50-original strain BI0 4.6 -acromelanic,homozygous affected BIO 50.54-agoute,homozygous affected BIO 82.62-acromelanic,homozygous affected BIO 53.58-homozygous affected b. Autosomal recessive skeletal muscle degeneration c. Serum levels of phosphocreatine kinase parallel the course of the disease and calcific tongue lesions are pathognomonic of the disease. d. also develop cardiomyopathy, cardiohypertrophy, and congestive heart failure-die by nine months of age Comparison: Good model for physiology and pathogenesis of Duchenne's dystrophy: variable sizes of muscle fiber, centrally located nuclei, with fatty infiltration and fibrous connective tissue replacement. Signs develop by sixty days of age. 3. Cholesterol Cholelithiasis in hamsters a. Human disease- Cholesterol cholelithiasis or gall stones b. Model description: 90% frequency occurs in hamsters within three months, when fed diets high in simple carbohydrates and free of fat and fiber. The model is useful for determining diets which induce the syndrome. 4. Periodontal disease in Chinese hamsters with concurrent diabetes mellitus a. Human disease: Periodontal disease b. Model description: Used to determine the influence of the anatomy of the alveolar processes on the morphology of bone destruction. To develop means of reducing the destruction of alveolar bone by decreasing osteoclastic activity. Diabetes in man also potentiates periodontal disease. 5. Anophthalmia in hamsters a. Human disease: Anophthalmia b. Model description: Occurs in hamsters with total albinism transmitted by a pair of incompletely dominant genes(Wh) homozygotes affected with a complete absence of the primary optic vesicle. 6. Polycystic diseases in hamsters a. Human disease: Polycystic kidneys b. Model description: Orignally detected polycystic disease in an NIH hamster colony. True cyst were manifested in the renal pelvis and other organs. 7. Cardiomyopathic Syrian hamster BIO (R)14.6 a. Human disease: Myocardial degeneration b. Model description: Myocardial necrosis begins as early as one month of age in this model, leading to ventricular failure and death within one year. Disease is thought to result from microvascular abnormalities. B. Induced Experimental Models of Human Disease 1. Lung diseases including emphysema in hamsters a. Human disease: Centrilobular emphysema b. Model description: Hamsters are used for inhalation studies using cigarette smoke, combustion engine exhaust, and other insults with resultant cases of induced emphysema and/or interstitial fibrosis. 2. Induced Arnold-Chiari Malformation(ACM) a. Human disease: ACM b. Model description: Disease in induced by administering a single dose of vitamin A to a pregnant hamster on the morning of the eighth day of gestation. Fetal maturation of the occipital bone is altered resulting in caudal herniation of the cerebellar tissue with subsequent onset of CNS compression and osseus changes similar to humans with the malady. C. OTHER EXPERIMENTAL USES 1. Induced caries in hamsters a. Human disease: Dental caries b. Model use: Study caries rates in Syrian hamsters influenced by the form of carbohydrates and the presence or absence of vitamins in the diet coupled with infectious processes. 2. Foriegn tissue transplantation: Since the cheek pouches do not have intact lymphatic drainage, they are an ideal site for tissue transplants, such as, tumors and grafts. 3. Radiobiology research: The Syrian and Chinese hamsters are among the most radio-resistant animals studied, with respect to lethality and survival time post exposure. 4. Parisitology research: The hamster has been used as a host for a variety of parasites, including but not limited to Entamoeba spp and Leishmania spp., for the purposed of diagnostics and study of their pathogenesis. 5. Viral Research: Hamsters are used extensively in slow virus(Scrapie,chronic measles,etc),type C Onco virus, influenza virus, respiratory syncytial virus studies and vaccine production (Foot & Mouth). 6. Hamsters are used for invivo and in vitro diagnostic techniques for numerous infectious agents (i.e. Clostridium spp.; Leptospirosis spp.). 7. Hypothermia research: When the hamster hibernates, the body temperature and other physiological parameters, such as heart rate, activity, and etc, decrease substantially. This makes it easy to study long term effects of hypothermia. Andrews E J; Ward BC; Altman N H; Spontaneous animal Models of Human Diseases;VOL I&II; ACLAMS.1979. Coggin J H; Koakes J E; Huebner R J; Gilden R; Unusual Filterable Oncogenic Agent Isolated From Horizontally Transmitted Syrian Hamster Lymphomas; Nature(LOND) 290 (5804) 1981.336-338 Factor S M; Minase T; Cho S;Dominitz R; Sonnenblick E H; Micro Vascular Spasm in the Cardio Myopathic Syrian Hamster: A preventable cause of focal Myo Cardial Necrosis. Circulation 66 (2). 1982.342-354. Feldman D B; McConnel E E; Knapka J J; Growth,Kidney Disease, and Longevity of Syrian Hamsters Fed Varying Levels of Protein. Lab Anim Sci 32(6) 1982. 613-618. Hoffman R A; The Golden Hamster. Iowa State ULniversity Press. 1968. Hoidal J R; Niewoehner D E; Cigarette Smoke Inhalation Potentiates Elastase Induced Emphysema in Hamsters. Am Rev Respir Dis 127 (4). 1983.478-481. Hoosier G L; Ladiges W C; Biology and Diseases of Hamsters. Laboratory Animal Medicine. Academic Press Inc. 1984. Lasfargues J-J; Saffar J-L; Effect of Indomethacin on Bone Destruction During Experimental Periodontal Disease in the Hamster. J Periodontal Res 18 (1). 1983. 110-117. Lentsch R H ; McLaughin R M; Wagner J E; Day T J; Campylobacter- Fetus-ssp-jejuni isolated from Syrian Hamsters with Proliferative Ileitis. Lab Anim Sci . 32(5). 1982. 511-514. Marin-Padilla M; Marin-Padilla T M; Morphogenisis of Experimentally Induced Arnold Chiari Malformation. J Neurol Sci 50 (1). 1981.29-56. Markris G P; Saffar J L; Architecture of the Alveolar Processes of the Hamster Jaw: Influence on the Localization and Morphology of Periodontal Diseases J Biol Buccale 10 (1) 1982. 31-34 Maxwell K O; Wish C; Murphy J C; Fox J G; Serum Chemistry Reference Values in Two Strains of Syrian Hamsters. Lab Anim Sci. 35 (1) 1985. 67-70. Onderdonk A B ; Brodasky T F; Bannister B; Comparative Effects of Clindamycin and Metabolites in the Hamster Model of Antibiotic Associated Colitis. J Antimicrob Chemother 8(5) 1981. 383-394. Rinaldo J; Goldstein R H; Snider G L; Modification of Oxygen Toxicity After Lung Injury by Bleomycin in Hamsters Mesocritcetus auratus. Am Rev Respir Dis 126 (6). 1982. 1030-1033.