BN

 

 

Genotype:

Pigmentation genes: aa BB CCHHPP RR

 

Mhc: RT1 ⁿ(RT1.AⁿB/DⁿCⁿ)

Erythrocyte antigens: RT2 ^a RT3 ^b RT8 ^b

Lymphocyte antigens: RT6 ^b RT7 ^a

 

 

Inbr. Gen.: At Han (1998), F 99.

 

Origin: Billingham and Silvers (Ss), 1958, from a brown mutation maintained by H. D. King and P. Aptekman in a pen-bred colony (5). To N in 1972 from Ss at F34 (16). To Han in 1972 from N at F51.

 

Lifespan: Virgin males 90% survival age, 25 months; 50% survival age, 32 months; 10% survival age, 38 months. Virgin females 90% survival age, 25 months; 50% survival age, 33 months; 10% survival age, 38 months. Retired breeder females 90% survival age, 26 months; 50% survival age, 35 months; 10% survival age, 40 months (8).

 

Reproduction: High rate of sterility, average effective breeding age 7-8 months, average litter size 5.43, productivity 0,43 young/female/week.

 

Tumours (Spontaneous): High incidence of tumours of the bladder (28-35% in males, 2-3% in females) and ureter (6-9% in males, 20-22% in females) (6, 8, 9). Other commonly found tumours in males pancreatic islet adenomas 15%, pituitary adenomas 14%, lymphoreticular sarcomas 14%, adrenal cortical adenomas 12%, medullary thyroid carcinomas 9%, adrenal pheo-chromocytomas 8%. Other commonly found tumours in females pituitary adenomas 26%, ureter carcinomas 22%, adrenal cortical adenomas 19%, cervical and vaginal sarcomas 19%, mammary gland fibroadenomas 11%, pancreatic islet cell adenomas 11%, adrenal cortical carcinomas 9% adrenal pheochromocytomas 7%, medullary thyroid carcinomas 6%, lymphoreticular sarcomas 6% (8, 9). Increased risk of development of cancer and metastasis in females with age (8).

 

Tumours (Induced): Dimethyl-benzanthracene induces transplantable, myeloid leukemia (12).

 

Other Characteristics: High incidence of endocardial disease in aged animals (7, 8). High incidence (31%) of hydronephrosis in 2-month-old BN/Bi rats reported by Cohen et al. (11). Little chronic progressive nephrosis seen in BN/Bi rats prior to 30 months of age, after which the disease progresses slowly (14). Resistant to induction of Heymann nephritis (2). Median lethal dose (LD50) of pentobarbital sodium 90 mg/kg (26). Resistant to induction of experimental allergic encephalomyelitis (EAE) by injection with guinea pig basic protein (13, 23); however, develop severe EAE when immunized with rat spinal cord and carbonyl iron adjuvant (20). Resistant to induction of autologous immune complex glomerulonephritis (30). T cells from lymph nodes of BN rats immunized with bovine P2, a peripheral nerve myelin protein, induce experimental allergic neuritis (EAN) in syngeneic recipients, overcoming the resistance of this strain to actively induced EAN (21). Do not produce anti-Ia antibodies. BN rats reject LEW fetal bone grafts, but LEW rats do not reject BN fetal bone grafts (25). Skin from neonatal males induces tolerance to subsequent grafts of male skin onto syngeneic females (27). Major histocompatibility complex (RT1) well studied (e.g., 1, 15, 17, 19, 22, 29). Low antibody response to concanavalin A, phytohemagglutinin, and streptococcal group A carbohydrate; not linked to RT1 (18, 28, 31). Substrains vary with respect to Pep-3 (3) and RT2 (24) probably due to residual heterozygosity before subline dichotomy. Genetic marker profile described by Bender et al. (1994) (4).

 

References:

 

1. 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.

 

2. Badalamenti, J., M. Shea, A. V. Cybulsky, R. J. Quigg, and D. J. Salant. 1987. Heymann nephritis (HN) antigen in Lewis (LEW) and Brown Norway (BN) rats. Fed. Proc. 46: 1327 (abstr.).

 

3. 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.

 

4. 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.

 

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

 

6. Boorman, G. A. and C. F. Hollander. 1974. Brief communication: High incidence of spontaneous urinary bladder and ureter tumors in the brown Norway rat. J. Natl. Cancer Inst. 52: 1005 1008.

 

7. Boorman, G. A., C. Zurcher, C. F. Hollander, and V. J. Feron. 1973. Naturally occurring endo-cardial disease in the rat. Arch. Pathol. 96: 39 45.

 

8. Burek, J. D. 1978. Pathology of Aging Rats. CRC Press, West Palm Beach, Fla. 230 pp.

 

9. Burek, J. D. and C. F. Hollander. 1977. Incidence patterns of spontaneous tumors in BN/Bi rats. J. Natl. Cancer Inst. 58: 99 105.

 

10. Burek, J. D., C. Zurcher, and C. Hollander. 1976. High incidence of spontaneous cervical and vaginal tumors in an inbred strain of Brown Norway rats BN/Bi. J. Natl. Cancer Inst. 57: 549 554.

 

11. Cohen, B. J., R. W. De Bruin, and W. J. Kort. 1970. Heritable hydronephrosis in a mutant strain of brown Norway rats. Lab. Anim. Care 20: 489 493.

 

12. Colly, L. P. and T. Hagenbeek. 1977. Experimental chemotherapy: A rat model for human acute myeloid leukemia. In S. J. Baum and D. G. Ledney, eds., Experimental Hematology Today, 211 219, Springer Verlag, New York.

 

13. 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.

 

14. Gray, J. E., M. J. van Zwieten, and C. F. Hollander. 1982. Early light microscopic changes of chronic progressive nephrosis in several strains of aging laboratory rats. J. Gerontol. 37: 142 150.

 

15. Günther, E., E. Rüde, and O. Stark. 1972. Antibody response in rats to the synthetic polypeptide (T,G)-A--L genetically linked to the major histocompatibility system. Eur. J. Immunol. 2: 151 155.

 

16. Hansen, C. T., S. Potkay, W. T. Watson, and R. A. Whitney, Jr. 1982. NIH Rodents: 1980 Catalogue. NIH Publ. No. 83 606, U.S. Department of Health and Human Services, Washington, D.C.

 

17. Koch, C. 1974. Inheritance in the rat of the antibody response to two different determinants of (T,G)-A--L. Immunogenetics 1: 118 125.

 

18. Koch, C. 1976. Genetic control of antibody responses to PHA in inbred rats. Scand. J. Immunol. 5: 1149 1153.

 

19. 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.

 

20. Levine, S. and R. Sowinski. 1975. Allergic encephalomyelitis in the reputedly resistant Brown Norway strain of rats. J. Immunol. 114: 597 601.

 

21. Linington, C., A. Mann, S. Izumo, K. Uyemura, M. Suzuki, R. Meyermann, and H. Wekerle. 1986. Induction of experimental allergic neuritis in the BN rat: P2 protein-specific T cells overcome resistance to actively induced disease. J. Immunol. 137: 3826 3831.

 

22. 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.

 

23. McFarlin, D. E., S. C.-L. Hsu, S. B. Slemenda, S. C.-H. Chou, and R. F. Kibler. 1975. The immune response against an encephalitogenic fragment of guinea pig basic protein in the Lewis and Brown Norway strains of rat. J. Immunol. 115: 1456 1458.

 

24. Paul, L. C. and C. B. Carpenter. 1981. Heterogeneity of inbred BN strain rats for the RT2 locus. Transplant. Proc. 13: 1497.

 

25. Segal, S., T. Siegal, H. Altaraz, A. Lev-El, Z. Nevo, L. Nebel, A. Katzenelson, and M. Feldman. 1979. Fetal bone grafts do not elicit allograft rejection because of protecting anti-Ia allo-antibodies. Implications to the immune survival of fetuses in allogeneic mothers. Transplantation 28: 88 95.

 

26. 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.

 

27. Silvers, W. K. and N. H. Collins. 1979. The behavior of H-Y-incompatible neonatal skin grafts in rats. Transplantation 28: 57 59.

 

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

 

29. Stark, O., B. Frenzl, and V. Kren. 1968. Erythrocyte and transplantation antigens in inbred strains of rats. VII. H-1 alleles of the LEP, CAP, BN, BD V, BD VII and BD X strains. Folia Biol. (Prague) 14: 169 175.

 

30. Stenglein, B., G. H. Thoenes, and E. Günther. 1975. Genetically controlled autologous immune complex glomerulonephritis in rats. J. Immunol. 115: 895 897.

 

31. Williams, R. M., M. J. Moore, and B. Benacerraf. 1973. Genetic control of thymus-derived cell function. III. DNA synthetic responses of rat lymph node cells stimulated in culture with concanavalin A and phytohemagglutinin. J. Immunol. 111: 1571 1578.

 

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