Biobreeding rat

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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[edit]

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[edit]

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

See also[edit]

References[edit]

  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