HAMSTERS BIOLOGY, CARE, DISEASES & MODELSI. INTRODUCTION/HISTORY A. Approximately 1,000,000 hamsters are used in researchannually in the united states. Of these, 90% are Syrian(Golden), Mesocrictus auratus, and the remainder are primarilythe Chinese(striped back), Cricetus griseus; the Armenian(gray),Cricetulus migratorius; and the European, Cricetus cricetus. By1971, the hamster had become the third most commonly usedlaboratory animal in the United States, exceeded only by mice andrats. B. Syrian hamsters, utilized as laboratory animals,originated from one litter captured in Syria in 1930. Only threemenbers of this litter were retained in captivity, and it is theprogeny of these that were first imported to the United States in1938. The four main reasons given for selection of the SyrianHamster for research are (1) availability and ease ofreproduction,(2) relative freedom from spontaneous diseasescoupled with susceptibility to many introduced pathogenic agents,(3) anatomical and physiological features with unique potentialfor study, and (4) rapid development with short life cycles. C. The Chinese hamster was first used as a laboratoryanimal in 1949. Since that time it has been used in severalaspects of infectious disease,radiobiological,endocrine,carcinogenic, and mutagenic research. Since the Chinese hamsterhas the lowest chromosome number of any other placental nurturedlab animal it is useful for cytogenesis research. D. The European hamster developed some laboratoryimportance when several wild animals caught in a West Germanindustrial area were found to have had bronchogenic squamous cellcarcinoma. This hamster has since been found to be susceptibleto N-diethylnitrosamine with the resultant development ofrespiratory tumors. It was concluded that the European hamsteris a more suitable model than the Syrian hamster for highlyconcentrated and prolonged smoke inhalation studies. Also theEuropeon hamster is much larger than other hamsterspecies(300-400 gm). E. The Armenian hamster was first introduced as alaboratory animal in 1963. It was selected because of itssusceptibility to mutagenic and carcinogenic agents and forstudying 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 theirnatural environment, hamsters live in deep tunnels that ensure acooler temperature and higher humidity than the general desertenvironment. B. GENETICS/ANATOMY 1. Taxonomy ORDER: Rodentia FAMILY: Cricetidae
GENUS: Mesocricetus SPECIE: auratus2. 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 Syrian4. Genotype- Diploid (2N) chromosome number: 445. Phenotypic Characteristics- The adult Syrianhamster is larger than a mouse, usually growing to 6 to8 inches in length and weighing from 110 to 140 gm. Itvirtually tailless, and has smooth, short hair. Normalcoloration is reddish-gold, with grayish-white ventralportion, however, color can range from albino to darkbrown (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 openingsC. 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 dont 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 natureD. 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 hamsters 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 hamsters 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 its 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 scrapingIII. CHINESE HAMSTER A. Native to the Eastern shore of China near the CaspianSea. They were first successfully bred in 1958, afterillumination 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 hamsterD. 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 Duchennes dystrophy: variable size