F344

 

Genotype:

Pigmentation genes: aa BB cc hh PP RR

 

Mhc: RT1 ^lv1(RT1.A^lB/D^lC^lv1)

 

Erythrocyte antigens: RT2 ^a RT8 ^b

 

Lymphocyte antigens: RT6 ^b RT7 ^a

 

Inbr. Gen.: At Ztm (1998), F168.

 

Origin: Curtis and Dunning, 1920, Columbia University Institute for Cancer Research. To Heston 1949 (13). To N in 1951 (29), to Han, to Ztm 1994.

 

Lifespan: Median lifespan 23-29 months in barrier-reared males (18,42, 57, 70) and 26-28 months in barrier reared females (42, 59). Restricted feeding (60% ad libitum intake) prolongs median lifespan to more than 34 months in males (70). Cameron et al. (16) found a 75% survival at 26 months of age.

 

Reproduction: Good reproductive performance; 0.79 young weaned per female per week; averge litter size at weaning 6,79. Males reach sexual maturity between 10 and 15 weeks, as determined by sperm production rate and other indicators of testicular and epididymal function (14).

 

Tumours (Spontaneous): Mammary tumours (females 41%, males 23%), pituitary adenomas (females 36%, males 24%) (57). Incidence of large granular lymphocyte (mononuclear cell) leukemia, 10-35% in animals over 18 months of age (61). Incidence of various other leukemias, 23-26% (19, 43, 53, 57). Incidence of testicular interstitial cell tumours 65-90% (17, 19, 43, 57). Thyroid carcinoma 22% (48). Uterine polyploid tumours of endometrial origin 21% (18). Incidence under germ-free conditions ? leukemia 26% in males, 36% in females; mammary tumours 12% in males, 20% in females; all other tumours 9% in males, 5% in females (56).

 

Tumours (Induced): F344 rats are commonly used in carcinogenesis research, and a great many tumours have been induced in this strain. Comparative studies show males more sensitive than BUF or Marshall rats to hepatocarcinogenic or cirrhotic effects of N-2-fluorenyldiacetamide; females more resistant to mammary tumourigenic effects of N-hydroxy-2-acetylfluorene than Sprague-Dawley or Wistar rats (20). More rapid absorption of implanted diethylstilbestrol than strains ACI and COP, leading to more rapid death with greatly enlarged pituitaries and fatty livers (21). Will grow Dunning, Novikoff, and LC-18 hepatomas; mammary carcinomas HMC and R-3230; mammary adenocarcinoma IRC-741; mammary fibroma F-609; uterine sarcoma F-529; pituitary tumours MtT and MtF.F4; Walker 256 carcino-sarcoma; Dunning, H6TF1, R3149, R3323, R3330, R3399, and R3432 leukemias; lymphosarcoma R-3251; fibrosarcoma R-3244; and sarcomas IRS-9802 and R3259 (29).

 

Other Pathology: Pathology of aged animals extensively characterized (18, 20, 26). Aged rats exhibit peripheral retinal degeneration characterized by selective loss of photoreceptor cells and formation of microcrystoids. The incidence and severity of the disease is increased by moderate (32 foot-candle) fluorescent light intensity (45). Aged rats exhibit cardiomyopathy characterized by myocardial degeneration, fibrosis, and chronic interstitial myocarditis (males 33%, females 18%) and nephropathy (males 67%, females 39%) (18, 26). Severity of nephropathy reduced by treatment with arylsulfonylurea (52). Most animals older than 24 months exhibit small, local areas of nephritis; less than 25% show severe nephritis (59). Urolithiasis can be induced in weanling rats by exposure to terephthalic acid or dimethyl terephthalate in the diet (68). p-Chloro-DL-phenylalanine plus L-phenylalanine induces phenylketonuria (1, 2). Bleomycin induces pulmonary fibrosis, which can be reduced by treatment with indomethacin (63).

 

Immunologic Characteristics: Resistant to spontaneous autoimmune thyroiditis (27). Susceptible to experimental allergic encephalomyelitis (23), experimental allergic neuritis (47), and autologous immune complex nephritis (67). Resistant to induction of thyroiditis by 3-methylcholanthrene (24). Resistant to group A Streptococcus pyogenes- and Lactobacillus casei-induced chronic poly-arthritis (46). The major histocompatibility complex (RT1) has been described (3, 44, 50). Low antibody response to streptococcal group A carbohydrate; not linked to RT1 (60). Low primary and secondary immune responses to sheep red blood cells (62). Poor producers of reaginic antibody in response to ovalbumin in aluminum hydroxide (54). Alphafetoprotein and albumin genes studied by Boulter and Sell and compared to those of ACI and BUF (15).

 

Behavioural Characteristics: Easily handled. Behavioural characteristics described by Harrington (30-41).

 

Other Characteristics: Males grow faster initially and then level off, whereas females grow more slowly and steadily; however, at 2 years of age females are still much lighter than males (16). Esterase alleles described by Womack (69). Hepatic microsomal activity before and after pre-treatment with phenobarbital well characterized (e.g., 20, 25, 55). Females resistant to the development of sodium chloride-induced hypertension (28). Median lethal dose (LD50) of pentobarbital sodium 70 mg/kg (58), Neurological toxicity of poly-brominated biphenyls and acrylamide described by Tilson and his coworkers (64-66). Hematological parameters described by Lovell et al. (49). Thyroxine (T4) and triiodothyronine (T3) levels measured at various ages by Waner and Nyska (71). Proposed as an animal model for studying cerebral ischemia (22) and central sleep apnea (51). Neonatal rats susceptible to induction of Borrelia burgdorferi-induced arthritic lesions resembling those found in human Lyme disease (4). Genetic marker profile described by Bender et al. (1994) (11).

 

References:

 

1. Andersen, A. E. 1982. Phenylketonuria, supplemental update to model no. 47. In C. C. Capen, D. B. Hackel, T. C. Jones, and G. Migaki, eds. Handbook: Animal Models of Human Disease, fascicle 11. Registry of Comparative Pathology, Armed Forces Institute of Pathology, Washington, D.C.

 

2. Andersen, A. and G. Guroff. 1974. Phenylketonuria. Comp. Pathol. Bull. 6:1 2.

 

3. Armerding, D., D. H. Katz, and B. Benacerraf. 1974. Immune response genes in inbred rats. I. Analysis of responder status to synthetic polypeptides and low doses of bovine serum albumin. Immunogenetics 1: 329 339.

 

4. Barthold, S.W., K. D. Moody, G. A. Terwilliger, R. O. Jacoby, and A. C. Steere. 1988. An animal model for Lyme arthritis. Ann. N. Y. Acad. Sci. 539:264 273.

 

5. Bazin, H., A. Beckers, G. Urbain-Vansanten, R. Pauwels, C. Bruyns, A. F. Tilkin, B. Platteau, and J. Urbain. 1978. Transplantable IgD immunoglobulin-secreting tumors in rat. J. Immunol. 121: 2077 2082.

 

6. Beckers, A., P. Querinjean, and H. Bazin. 1974. Allotypes of rat immunoglobulins-II. Distri-bution of the allotypes of kappa and alpha chain loci in different inbred strains of rats. Immunochemistry 11: 605 609.

 

7. Beckers, A. and H. Bazin. 1978. Incidence of spontaneous ileocecal immunocytomas in hybrids of LOU/C rats and rat strains with low spontaneous tumor incidence: Brief communication. J. Natl. Cancer Inst. 60: 1505 1508.

 

8. Beierwaltes, W. H. and W. J. Arendshorst. 1978. Renal function of conscious spontaneously hypertensive rats. Circ. Res. 42: 721 726.

 

9. Belledonne, M., J. M. Preuss, and H. G. Preuss. 1979. Acid excretion in young and adult Wistar Kyoto and spontaneously hypertensive rats. Experientia 35: 1594?1595.

 

10. Bender, K., M. Adams, P. R. Baverstock, M. den Bieman, S. Bissbort, R. Brdicka, G. W. Butcher, D. V. Cramer, O. von Deimling, M. F. W. Festing, E. Günther, R. D. Guttmann, H. J. Hedrich, P. B. Kendall, R. Kluge, R. Moutier, B. Simon, J. E. Womack, J. Yamada, and B. van Zutphen. 1984. Biochemical markers in inbred strains of the rat (Rattus norvegicus). Immunogenetics 19: 257 266.

 

11. Bender, K., P. Balogh, M.F. Bertrand, M. den Bieman, O. van Deimling, S. Eghtessadi, G.A. Gutman, H. J. Hedrich, S.V. Kluge, K. Matsumoto, D.H. Moralejo, M. Nagel, A. Portal, C.-M. Prokop, R.T. Seibert and L.F.M. van Zutphen. 1994. Genetic characterization of inbred strains of the rat (Rattus norvegicus). I. Exp. Anim. Sci. 36: 151-166.

 

12. Berman, J. J., J. M. Rice, M. L. Wenk, and P. P. Roller. 1979. Intestinal tumors induced by a single intraperitoneal injection of methyl (acetoxymethyl) nitrosamine in three strains of rats. Cancer Res. 39: 1462 1466.

 

13. Billingham, R. E. and W. K. Silvers. 1959. Inbred animals and tissue transplantation immunity. Transplant. Bull. 6: 399 406.

 

14. Blazak, W. F., T. L. Ernst, and B. E. Stewart. 1985. Potential indicators of reproductive toxicity: Testicular sperm production and epididymal sperm number, transit time, and motility in Fischer 344 rats. Fund. Appl. Toxicol. 5: 1097 1103.

 

15. Boulter, J. and S. Sell. 1984. Polymorphism of rat alphafetoprotein and albumin genes. Tumour Biol. 5: 365 370.

 

16. Cameron, T. P., R. L. Hickman, M. R. Kornreich, and R. E. Tarone. 1985. History, survival, and growth patterns of B6C3F1 mice and F344 rats in the National Cancer Institute carcinogenesis testing program. Fundam. Appl. Toxicol. 5: 526 538.

 

17. Cockrell, B. Y. and F. M. Garner. 1976. Interstitial cell tumor. Comp. Pathol. Bull. 8: 2 3.

 

18. Coleman, G. L., S. W. Barthold, G. W. Osbaldistan, S. J. Foster, and A. M. Jonas. 1977. Pathological changes during aging in barrier-reared Fischer 344 male rats. J. Gerontol. 32: 258 278.

 

19. Davey, F. R. and W. C. Moloney. 1970. Postmortem observations of Fischer rats with leukemia and other disorders. Lab. Invest. 23: 327 334.

 

20. Dent, J. G., M. E. Graichen, S. Schnell, and J. Lasker. 1980. Constitutive and induced hepatic microsomal cytochrome P-450 monooxygenase activities in male Fischer-344 rats and CD rats. A comparative study. Toxicol. Appl. Pharmacol. 52: 45 53.

 

21. Dunning, W. F., M. R. Curtis, and A. Segaloff. 1947. Strain differences in response to diethylstilbestrol and the induction of mammary gland and bladder cancer in the rat. Cancer Res. 7: 511 521.

 

22. Duverger, D. and E. T. MacKenzie. 1988. The quantification of cerebral infarction following focal ischemia in the rat: Influence of strain, arterial pressure, blood glucose concentration, and age. J. Cereb. Blood Flow Metab. 8: 449 461.

 

23. Gasser, D. L., J. Palm, and N. K. Gonatas. 1975. Genetic control of susceptibility to experimental allergic encephalomyelitis and the Ag-B locus of rats. J. Immunol. 115: 431 433.

 

24. Glover, E. L., M. D. Reuber, and E. F. Godfrey. 1969. Methylcholanthrene-induced thyroiditis. Susceptibility of Buffalo strain rats. Arch. Environ. Health 18: 901 903.

 

25. Gold, G. and C. C. Widnell. 1975. Response of NADPH cytochrome C reductase and cytochrome P-450 in hepatic microsomes to treatment with phenobarbital ? Differences in rat strains. Biochem. Pharmacol. 24: 2105 2106.

 

26. Goodman, D.G., J. M. Ward, R. A. Squire, K. C. Chu, and M. S. Linhart. 1979. Neoplastic and nonneoplastic lesions in aging F344 rats. Toxicol. Appl. Pharmacol. 48: 237 248.

 

27. Hajdu, A. and G. Rona. 1969. Spontaneous thyroiditis in laboratory rats. Experientia 25: 1325 1327.

 

28. Hall, C. E., S. Ayachi, and O. Hall. 1976. Immunity of Fischer 344 rats to salt hypertension. Life Sci. 18: 1001 1007.

 

29. Hansen, C. T., F. J. Judge, and R. A. Whitney. 1973. Catalogue of NIH Rodents. DHEW Publ. No. 74 606. U.S. Department of Health, Education, and Welfare, Washington, D.C.

 

30. Harrington, G. M. 1971. Strain differences among rats initiating exploration of differing environments. Psychon. Sci. 23: 348 349.

 

31. Harrington, G. M. 1971. Strain differences in rotating wheel activity of the rat. Psychon. Sci. 23: 363 364.

 

32. Harrington, G. M. 1972. Strain differences in open-field behavior of the rat. Psychon. Sci. 27: 51 53.

 

33. Harrington, G. M. 1979. Strain differences in open-field behavior of the rat. II. Bull. Psychon. Soc. 13: 85 86.

 

34. Harrington, G. M. 1979. Strain differences in activity of the rat in a shuttle stabilimeter. Bull. Psychon. Soc. 13: 149 150.

 

35. Harrington, G. M. 1979. Strain differences in activity of the rat using a home cage stabilimeter. Bull. Psychon. Soc. 13: 151 152.

 

36. Harrington, G. M. 1979. Strain differences in free operant leverpress levels in the rat. Bull. Psychon. Soc. 13: 153 154.

 

37. Harrington, G. M. 1979. Strain differences in light-contingent barpress behavior of the rat. Bull. Psychon. Soc. 13: 155 156.

 

38. Harrington, G. M. 1979. Strain differences in passive avoidance conditioning in the rat. Bull. Psychon. Soc. 13: 157 158.

 

39. Harrington, G. M. 1979. Strain differences in runway learning in the rat. Bull. Psychon. Soc. 13: 159 160.

 

40. Harrington, G. M. 1979. Strain differences in shuttle avoidance conditioning in the rat. Bull. Psychon. Soc. 13: 161 162.

 

41. Harrington, G. M. 1979. Strain differences in simple operant barpress acquisition to an auditory stimulus by rats. Bull. Psychon. Soc. 13: 163 164.

 

42. Hoffman, H. J. 1979. Survival distributions for selected laboratory rat strains and stocks. In D. C. Gibson, R. C. Adelman, and C. Finch, eds., Development of the Rodent as a Model System of Aging, Book II, DHEW Pub. No. (NIH) 79 161, 19 34, U.S. Department of Health, Education, and Welfare, Washington, D.C.

 

43. Jacobs, B. B. and R. A. Huseby. 1967. Neoplasms occurring in aged Fischer rats, with special reference to testicular, uterine, and thyroid tumours. J. Natl. Cancer Inst. 39: 303 307.

 

44. Kunz, H. W., T. J. Gill III, and B. Borland. 1974. The genetic linkage of the immune response of poly(Glu52Lys33Tyr15) to the major histocompatibility locus in inbred rats. J. Immunogenet. 1: 277 287.

 

45. Lai, Y.-L., R. O. Jacoby, and P. C. Yao. 1979. Peripheral retinal degeneration in rats. Am. J. Pathol. 97: 449 452.

 

46. Lehman, T. J. A., J. B. Allen, P. H. Plotz, and R. L. Wilder. 1984. Lactobacillus-casei cell wall-induced arthritis in rats. Cell-wall fragment distribution and persistence in chronic arthritis-susceptible LEW/N and arthritis-resistant F344/N rats. Arthritis Rheum. 27: 939 942.

 

47. Levine, S. and E. J. Wenk. 1968. The production and transfer of allergic adrenalitis. Am. J. Pathol. 52: 41 53.

 

48. Lindsay, S., C. W. Nichols, Jr., and I. L. Chaikoff. 1968. Naturally occurring thyroid carcinoma in the rat. Similarities to human medullary carcinoma. Arch. Pathol. 86: 353 364.

 

49. Lovell, D. P., R. K. Archer, J. Riley, and R. K. Morgan. 1981. Variation in haematological parameters among inbred strains of rats. Lab. Anim. (London) 15: 243 249.

 

50. Luderer, A. A., P. H. Maurer, and R. T. Woodland. 1976. Genetic control of the immune response in rats to the known sequential polypeptide (Tyr-Glu-Ala-Gly)n. I. Antibody responses. J. Immunol. 117: 1079 1084.

 

51. Mendelson, W. B., J. V. Martin, M. Perlis, H. Giesen, R. Wagner, and S. I. Rapoport.1988. Periodic cessation of respiratory effort during sleep in adult rats. Physiol. Behav. 43: 229 234.

 

52. Milman, H. A., J. C. Peckham, J. M. Ward, and R. E. Tarone. 1979. Reduction of the severity of nephropathy in aging Fischer 344 rats treated with analogs of arylsulfonylurea. Toxicol. Appl. Pharmacol. 49: 425 430.

 

53. Moloney, W. C., A. E. Boschetti, and V. P. King. 1970. Spontaneous leukemia in Fischer rats. Cancer Res. 30: 41 43.

 

54. Murphey, S. M., S. Brown, N. Miklos, and P. Fireman. 1974. Reagin synthesis in inbred strains of rats. Immunology 27: 245 253.

 

55. Page, J. G. and E. S. Vesell. 1969. Hepatic drug metabolism in ten strains of Norway rat before and after pretreatment with phenobarbital. Proc. Soc. Exp. Biol. Med. 131: 256 261.

 

56. Sacksteder, M. R. 1976. Brief communication: Occurrence of spontaneous tumors in the germfree F344 rat. J. Natl. Cancer Inst. 57: 1371 1373.

 

57. Sass, B., L. S. Rabstein, R. Madison, R. M. Nims, R. L. Peters, and G. J. Kelloff. 1975. Incidence of spontaneous neoplasms in F344 rats throughout the natural life-span. J. Natl. Cancer Inst. 54: 1449 1456.

 

58. Shearer, D., D. Creel, and C. E. Wilson. 1973. Strain differences in the response of rats to repeated injections of pentobarbital sodium. Lab. Anim. Sci. 23: 662 664.

 

59. Snell, K. C. 1967. Renal disease of the rat. In E. Cotchin and F. J. Roe, eds. , Pathology of Laboratory Rats and Mice, 105 147, Blackwell Scientific Publications, Oxford.

 

60. Stankus, R. P. and G. A. Leslie. 1976. Rat interstrain antibody response and crossidiotypic specificity. Immunogenetics 3: 65 73.

 

61. Stromberg, P. C. 1985. Large granular lymphocyte leukemia. Am. J. Pathol. 119: 517 519.

 

62. Tada, N., K. Itakura, and M. Aizawa. 1974. Genetic control of the antibody response in inbred rats. J. Immunogenet. 1: 265 275.

 

63. Thrall, R. S., J. R. McCormick, R. M. Jack, R. A. McReynolds, and P. A. Ward. 1979. Bleomycin-induced pulmonary fibrosis in the rat. Inhibition by indomethacin. Am. J. Pathol. 95: 117 130.

 

64. Tilson, H. A. and P. A. Cabe. 1979. The effects of acrylamide given acutely or in repeated doses on fore- and hindlimb function of rats. Toxicol. Appl. Pharmacol. 47: 253 260.

 

65. Tilson, H. A. and P. A. Cabe. 1979. Studies on the neurobehavioral effects of polybrominated biphenyls in rats. Ann. N.Y. Acad. Sci. 320: 325 336.

 

66. Tilson, H. A., P. A. Cabe, and C. L. Mitchell. 1978. Behavioral and neurological toxicity of polybrominated biphenyls in rats and mice. Environ. Health Perspect. 23: 257 263.

 

67. Watson, J. I. and F. J. Dixon. 1966. Experimental glomerulonephritis. IX. Factors influencing the development of kidney in adjuvant nephritis in rats. Proc. Soc. Exp. Biol. Med. 121: 216 223.

 

68. Wolkowski-Tyl, R., T. Y. Chin, J. A. Popp, and H. d'A Heck. 1982. Urolithiasis. Am. J. Pathol. 107: 419 421.

 

69. Womack, J. E. 1973. Biochemical genetics of rat esterases: Polymorphism, tissue expression, and linkage at four loci. Biochem. Genet. 9: 13 24.

 

70. Yu, B. P., E. J. Masoro, I. Murata, H. A. Bertrand, and F. T. Lynd. 1982. Life span study of SPF Fischer 344 male rats fed ad libitum or resticted diets: Longevity, growth, lean body mass and disease. J. Gerontol. 37: 130 141.

 

71. Waner, T. and A. Nyska. 1988. Thyroxine (T4) and triiodothyronine (T3) levels in the Fischer 344 inbred rat. Lab. Anim. (London) 22: 276 280.