The BB rat spontaneously develops insulin-dependent diabetes mellitus of autoimmune etiology. From breeding studies, one of the genes necessary for the development of diabetes in these animals is linked to RT1, the rat major histocompatibility complex. To better define the BB rat's RT1-linked diabetogenic gene (RT1-DM), we have used restriction endonucleases BamH1 and EcoR1 in conjunction with an I-A alpha (class II mouse major histocompatibility complex) gene probe to study RT1 class II gene polymorphisms among diabetes-prone BB rats and the related non-diabetes-prone BBN rats. Both BB and BBN rats are indistinguishable RT1U by serologie methods. Four polymorphic chromosome types (la, lb, Ha, and lib) were recognized among the control BBN rats. In contrast, all BB rats were homozygous (IIa/IIa). From the multiple breeding programs involved, we hypothesize that the BB rat's RT1-linked diabetogenic gene is linked to an I-A alpha-defined gene of the type Ha chromosome. The ability to split the RT1U of BB rats will provide a powerful tool to localize and characterize RT1-DM.

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