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BB

Inbr. F30.

Colour: Albino,

Genet. c.

Origin: Mutation causing diabetes mellitus in a closed colony of outbred Wistar rats at Bio-Breeding Labs, Ontario, Canada in 1974 (Chappel and Chappel 1983). To Worcester in 1977 where inbreeding began. Sublines of diabetic-prone and diabetic-resistant animals have been developed, and there are also subline differences in the incidence, age of onset, untreated survival time of diabetes, leucopenia and body weight gain which can be attributed to genetic factors (Kloting et al 1987). A detailed study of 24 inbred and two outbred lines of diabetes-prone and diabetes resistant BB rats using eight marker loci found substantial genetic variation among and some variation within some of the colonies. The 22 colonies which were apparently isogenic could be divided into four groups on the basis of the marker loci (Prins et al 1990).

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Characteristics

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Reproduction:

average litter size at weaning 6.5 pups for diabetic-prone and 7.2 pups for the diabetic-resistant colonies.

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Lifespan and spontaneous disease

Abrupt onset of insulin-dependent, ketosis-prone diabetes between 60 and 120 days of age. Animals exhibit lymphocyte insulinitis with virtually complete destruction of pancreatic beta cells; T cell lymphopenia; lymphocytic thyroiditis, and autoantibodies to smooth muscle, thyroid colloid, and gastric parietal cells. T cell lymphopenia is due largely to the absence of RT6+ peripheral T cell subset, including members of both helper/inducer and suppressor/cytotoxic antigenic phenotypes (Greiner et al 1986). Isolated, perfused kidneys from diabetic animals show higher basal renin release and kidney renin content than kidneys from nondiabetic controls. Renin-secretory response to beta-adrenergic stimulation impaired (Cohen et al 1986). About 32% of diabetic rats develop gastric erosions and ulcerations compared with only 10% of non-diabetic BB rats (Wright et al 1981). Further discussions of the characteristics of this model are given in Metabolism 32 no 7 suppl.1, (1983) and in Mordes et al (1987). Poly I:C accelerates the development of diabetes both in diabetes-prone and resistant substrains (Sobel et al 1992, Ewel et al 1992). The development of lymphocytic thyroiditis is not affected by iodine treatment according to Allen (1992), though Ebner et al (1992) found that it does have some affect. Epitope specificities of collagen-induced arthritis studied by Cremer et al (1992). A lymphopenic, nondiabetic substrain BB-DR has very low T-cell numbers, depressed B-lymphocyte numbers and a complete absence of peripheral CD8+ T cells characteristics of the susceptible BB strain (Joseph et al 1993). Transfusing of BB-DR thymocytes into nude rats transfers the autoimmune insulin-dependent diabetes mellitus (Whalen et al 1995). The percentage of animals getting diabetes by 200 days of age depends on the sex distribution within litters and the phenotype of the parents. A maximum liklihood model for predicting the incidence of diabetes each generation has been developed by Vogt and Kloting (1993). In-vitro study of perfused islets suggested that diabetes is due to a reduction on beta cell mass (Teruya et al 1993). Endothelin urinary excretion is increased in diabetic BB rats (Morabito et al 1994).

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Drugs and chemicals

The sulfonylurea drug glipizide delays onset and decreases the incidence of diabetes (Hosszufalusi et al 1994).

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Allen E. M. (1992) The effect of iodine on lipid-peroxidation and ultrastructure in the thyroids of BB/Wor rats. Journal of Endocrinological Investigation 15, 519-523. \par

Chappel C. I. and Chappel W. R. (1983) The discovery and development of the BB rat colony: An animal model of spontaneous diabetes mellitus. Metabolism 32, S8-S10. \par

Cohen A. J., McCarthy D. M., and Rossetti R. R. (1986) Renin secretion by the spontaneously diabetic rat. Diabetes 35, 341-346. \par

Cremer M. A., Terato K., Watson W. C., Griffiths M. M., Townes A. S., and Kang A. H. (1992) Collagen-induced arthritis in rats - examination of the epitope specificities of circulating and cartilage-bound antibodies produced by outbred and inbred rats using cyanogen bromide-derived peptides purified from heterologous and homologous type-II collagens. J. Immunol. 149, 1045-1053. \par

Ebner S. A., Lueprasitsakul W., Alex S., Fang S. L., Appel M. C., and Braverman L. E. (1992) Iodine content of rat thyroglobulin affects its antigenicity in inducing lymphocytic thyroiditis in the BB/Wor rat. Autoimmunity 13, 209-214. \par

Ewel C. H., Sobel D. O., Zeligs B. J., and Bellanti J. A. (1992) Poly-I-C accelerates development of diabetes-mellitus in diabetes-prone BB rat. Diabetes 41, 1016-1021. \par

Greiner D. L., Handler E. S., Nakano K., Mordes J. P., and Rossini A. A. (1986) Absence of the RT-6 T cell subset in diabetes-prone BB/W rats. J. Immunol. 136, 148-151. \par

Hosszufalusi N., Reinherz L., Takei S., Chan E., and Charles M. A. (1994) Glipizide-induced prevention of diabetes and autoimmune events in the BB rat. Journal of Autoimmunity 7, 753-761. \par

Joseph S., Diamond A. G., Smith W., Baird J. D., and Butcher G. W. (1993) BB-DR Edinburgh - a lymphopenic, nondiabetic subline of BB rat. Immunol. 78, 318-328. \par

Kloting I., Vgt L., Stark O., and Fischer U. (1987) Genetic heterogeneity in different BB rat subpopulations. Diabet. Res. 6, 145-149. \par

Morabito E., Corsico N., and Martelli E. A. (1994) Endothelins urinary-excretion is increased in spontaneously diabetic rats - BB/BB. Life Sciences 56, PL13-PL18. \par

Mordes J. P., Desemone J., and Rossini A. A. (1987) The BB rat. Diab. Metab. Rev. 3, 725-750. \par

Prins J. B., Herberg L., den Bierman M., and van Zutphen L. F. M. (1990) Genetic variation within and between lines of diabetes-prone and non-diabetes-prone BB rats; allele distribution of 8 protein markers. Lab. Anim. 25, 207-211. \par

Sobel D. O., Newsome J., Ewel C. H., Bellanti J. A., Abbassi V., Creswell K., and Blair O. (1992) Poly-I-C induces development of diabetes-mellitus in BB rat. Diabetes 41, 515-520. \par

Teruya M., Takei S., Forrest L. E., Grunewald A., Chan E. K., and Charles M. A. (1993) Pancreatic-islet function in nondiabetic and diabetic BB rats. Diabetes 42, 1310-1317. \par

Vogt L. and Kloting I. (1993) Model-based prediction of diabetes incidence in BB/Ok rats. Diabete & Metabolisme 19, 183-187. \par

Whalen B. J., Rossini A. A., Mordes J. P., and Greiner D. L. (1995) DR-BE rat thymus contains thymocyte populations predisposed to autoreactivity. Diabetes 44, 963-967. \par

Wright J. R., Yates A. J., Sharman H. M., and Thibert P. (1981) Spontaneous gastric erosions and ulcerations in BB Wistar rats. Lab. Animal Sci. 31, 63-66. \par

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INBRED STRAINS OF RATS
Updated 9 Apr. 1998
Michael FW Festing
MRC Toxicology Unit, Hodgkin Building,
University of Leicester, UK