Biobreeding rat

Biobreeding rat also known as the BB or BBDP rat is an inbred laboratory rat strain that spontaneously develops autoimmune Type 1 Diabetes. Like the NOD mice, BB rats are used as an animal model for Type 1 diabetes. The strain re-capitulates many of the features of human type 1 diabetes, and has contributed greatly to the research of T1D pathogenesis.[1]

Two T1D susceptibility genes have been identified in the BB rat. The susceptible MHC class II RT1u haplotype on chromosome 20 [2] and a null mutation in the GIMAP5 gene on chromosome 4.[3] The Gimap5 mutation results in severe T cell lymphopenia in the BB rat and is thought to contribute to T1D pathogenesis through impaired development and function and regulatory T cells.[4] Recently, 8 additional loci on rat chromosomes 1,2,3,6 (2 loci), 12 and 14 have been shown to be linked to Type 1 Diabetes in the BB rat.[5]

History

BB rats are the most extensively studied rat model of T1D. They were originally derived from a Canadian colony of outbred Wistar rats that spontaneously develop hyperglycemia and ketoacidosis, characteristic of clinical onset of T1D.[6] Subsequent BB rat colonies were established. One in Worcester, Massachusetts, has been inbred and known as BBDP/Wor and another one in Ottawa, Canada, an outbred strain known as BBdp.[7]

Modulation of diabetes

Diabetes in BB rats can be prevented by a single injection of mycobacterial adjuvants such as complete Freund's adjuvant (FCA).[8]

See also

References
  1. Mordes JP, Poussier P, Blankenhorn EP, Greiner DL: Rat models of type 1 diabetes: Genetics, environment and autoimmunity. Boca Raton, CRC Press, 2007
  2. Colle, E., R.D. Guttmann, and T. Seemayer, Spontaneous diabetes mellitus syndrome in the rat. I. Association with the major histocompatibility complex. The Journal of experimental medicine, 1981. 154(4): p. 1237-42.
  3. Poussier, P., et al., Lymphopenia and abnormal lymphocyte subsets in the "BB" rat: relationship to the diabetic syndrome. Endocrinology, 1982. 110(5): p. 1825-7.
  4. Poussier, P., et al., Impaired post-thymic development of regulatory CD4+25+ T cells contributes to diabetes pathogenesis in BB rats. Journal of Immunology, 2005. 174(7): p. 4081-9.
  5. Wallis RH, Wang K, Marandi L, Hsieh E, Ning T, Chao GY, Sarmiento J, Paterson AD, Poussier P.: Type 1 diabetes in the BB rat: a polygenic disease. Diabetes. 2009 Apr;58(4):1007-17. Epub 2009 Jan 23
  6. Mordes, J.P., et al., Rat models of type 1 diabetes: genetics, environment, and autoimmunity. ILAR J, 2004. 45(3): p. 278-91.
  7. Mordes, J.P., et al., Rat models of type 1 diabetes: genetics, environment, and autoimmunity. ILAR J, 2004. 45(3): p. 278-91.
  8. Sadelain MW, Qin HY, Sumoski W, Parfrey N, Singh B, Rabinovitch A. Prevention of diabetes in the BB rat by early immunotherapy using Freund's adjuvant. J Autoimmun; 1990 ; 3:671-80. PMID 2088390
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