Genet. a, b, hi.
Origin: Billingham and Silvers 1958, from a brown mutation maintained by DH King and P Aptekman in a pen-bred colony (Billingham and Silvers 1959). A plasma kininogen-deficient mutant strain (BN/Ka) has been described in which release of heat-induced substance P is defective (Tang et al, 1994) and response to the hypertensive effects of deoxycorticosterone acetate salt is much faster than in normal BN rats (Majima et al, 1995a,b).
Pathology and spontaneous disease
Endocardial disease 7% at an average age of 31 months (Boorman et al 1973). Tumours of epithelium 28% in males, 2% in females. Ureter tumours 20% in females, 6% in males. Estimated median life-span more than 24 months in males and more than 25 months in females (Boorman and Hollander 1974).
Median lifespan 29 months in males (n=74) and 31 months in females (n=236). Most common neoplastic lesions in males were urinary bladder carcinoma 35%, pancreas islet adenoma 15%, pituitary adenoma 14%, lymphoreticular sarcoma 14%, adrenal cortex adeneoma 12%, medullary thyroid carcinoma 9%, adrenal pheochromocytoma 8%. Four other types of tumours were observed. In females: pituitary adenoma 26%, ureter carcinoma 22%, adrenal cortical adenoma 19%, cervix sarcoma 15%, mammary gland fibroadenoma 11%, islet adenoma 11%. Twelve other tumour types were observed (Burek and Hollander 1975a).
The chance of death from metastases increased with age in females, but reaches a peak at 25-30 months in males (Burek and Hollander 1975b). The cervical and vaginal tumours have been studied in more detail by Burek et al (1975a), and further details of an aging colony are given by Hollander (1976) and Burek and Hollander (1977). Vaginal and cervical tumours, mostly sarcomas but also seven squamous-cell carcinomas and four leiomyomas, were seen in 20% of animals that died naturally (Burek et al 1976). High incidence (31%) of hydronephrosis reported in 2-month-old BN/Bi (Cohen et al 1970), but little seen by Gray et al (1982) before 30 months, after which the disease progressed slowly. A high incidence was observed at all ages by Spangler et al (1994).
Moderately sensitive to the development of experimental glomerulonephritis following injection of nephritogenic antigen from bovine renal basement membrane (Naito et al, 1991)
Develops severe experimental allergic encephalomyelitis when immunised with rat spinal cord and carbonyl iron adjuvent (Levine and Sowinski 1975). Linington et al (1986) induced experimental allergic neuritis using T-cells and bovine P2 (a peripheral nerve myelin protein). Resistant to the induction of Haymann nephritis (Badalamenti et al 1987). High IgE response to Japanese Cedar pollen antigen (1/7): may be a useful model for studying physiological and pathological changes in the nose after pollen challenge (Imaoka et al, 1993). Resident macrophages (ramified microglea) of the central nervous system are constitutively major histocompatibility complex class-II positive, in contrast with LEW (Sedgwick et al, 1993). Following lethal irradiation and re-constitution with syngeneic bone marrow and given cyclosporin A for several weeks LEW rats will develop cyclosporin-induced autoimmunity after withdrawal of the cyclosporin. The condition resembles graft-versus host disease in terms of acute dermatitis and chronic scleroderma. However, BN rats do not develop this disease (Wodzig et al, 1993). Resistant to the induction of experimental autoimmune uveoretinitis and endotoxin-induced uveitis which appears to be associated with the production of tumour necrosis factor (TNF) by retinal Muller glia and retinal pigmented epithelium. Strain LEW is susceptible (Dekozak et al, 1994). Susceptible to the induction of proteinuria following treatment with the monoclonal antibody 5-6-1, like LEW and outbred Wistar, but unlike resistant outbred Sprague-Dawley rats which were also resistant to glomerular damage (Gollner et al, 1995).
Low antibody response to phytohaemagglutinin, concanavalin A and streptococcal group A carbohydrate (Koch 1976, Stankus and Leslie 1976, Williams et al 1973). Good (1/5) antibody response to a synthetic 20 amino acid peptide derived from the alpha helical region of the RT1-D-u beta chain (Murphy et al, 1994).
Burek J. D. and Hollander C. F. (1975a) Studies of spontaneous lesions in aging BN/Bi rats. I. Neoplastic and non-neoplastic lesions, in Annual Report, Organization for Health Research, pp. 235-237. TNO, Rijswijk. \par
Burek J. D. and Hollander C. F. (1975b) Studies of spontaneous lesions in aging BN/Bi rats. II. Age associated incidence of tumors and tumor metastases, in Annual Report, Organization for Health Research, pp. 238-241. TNO, Rijswijk. \par
Colly L. P. and Hagenbeek T. (1977) Experimental chemotherapy: A rat model for human acute myeloid leukemia, in Experimental hematology today (Baum S. J. and Ledney D. G., eds), pp. 211-219. Springer Verlag, New York. \par
Dekozak Y., Naud M. C., Bellot J., Faure J. P., and Hicks D. (1994) Differential tumor-necrosis-factor expression by resident retinal cells from experimental uveitis-susceptible and uveitis-resistant rat strains. J. Neuroimmunol. 55, 1-9. \par
Gollner D., Kawachi H., Oite T., Oka M., Nagase M., and Shimizu F. (1995) Strain variation in susceptibility to the development of monoclonal- antibody 5-1-6-induced proteinuria in rats. Clin. Exp. Immunol. 101, 341-345. \par
Imrich H., Schwender S., Hein A., and Dorries R. (1994) Cervical lymphoid-tissue but not the central-nervous-system supports proliferation of virus-specific T-lymphocytes during coronavirus- induced encephalitis in rats. J. Neuroimmunol. 53, 73-81. \par
Kosuda L. L., Hosseinzadeh H., Greiner D. L., and Bigazzi P. E. (1994) Role of RT6(+) T-lymphocytes in mercury-induced renal autoimmunity -experimental manipulations of susceptible and resistant rats. J. Toxicol. Environ. Health 42, 303-321. \par
Linington C., Mann A., Izumo S., Uyemura K., Suzuki M., Meyermann R., and Wekerle H. (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. \par
Majima M., Adachi K., Kuribayashi Y., Mizogami S., and Katori M. (1995a) Increase in vascular sensitivity to angiotensin-II and norepinephrine after 4-day infusion of 0.3 m sodium-chloride in conscious kininogen- deficient Brown-Norway Katholiek rats. Jpn. J. Pharmacol. 69, 149-158. \par
McFarlin D. E., Hsu S. C.-L., Slemenda S. B., Chou S. C.-H., and Kibler and R. F. (1975a) 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. \par
Naito I., Kagawa M., Sado Y., and Okigaki T. (1991) Strain specific responses of inbred rats on the severity of experimental autoimmune glomerulonephritis - presence of a broad- spectrum of the susceptibility. International Journal of Immunopathology and Pharmacology 4, 145-154. \par
Peers S. H., Duncan G. S., Flower R. J., and Bolton C. (1995) Endogenous corticosteroids modulate lymphoproliferation and susceptibility to experimental allergic encephalomyelitis in the Brown-Norway rat. International Archives of Allergy and Immunology 106, 20-24. \par
Sedgwick J. D., Schwender S., Gregersen R., Dorries R., and Termeulen V. (1993) Resident macrophages (ramified microglia) of the adult Brown Norway rat central-nervous-system are constitutively major histocompatibility complex class-II positive. J. Exp. Med. 177, 1145-1152. \par
Williams R. M., Moore M. J., and Benacerraf B. (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. \par
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