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Specific class II histocompatibility gene polymorphism in BB rats.

J B Buse, A Ben-Nun, K A Klein

    Diabetes
    |July 1, 1984
    PubMed
    Summary
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    Researchers identified a specific gene linked to diabetes in BB rats. This gene, associated with the RT1 major histocompatibility complex, is crucial for understanding autoimmune diabetes development in these animals.

    Area of Science:

    • Immunogenetics
    • Endocrinology
    • Animal Models of Disease

    Background:

    • The BB rat is a model for spontaneous autoimmune diabetes.
    • A gene linked to the RT1 major histocompatibility complex (MHC) is implicated in diabetes development.
    • BB and BBN rats share the RT1u haplotype, making MHC-linked gene identification challenging.

    Purpose of the Study:

    • To define the RT1-linked diabetogenic gene (RT1-DM) in BB rats.
    • To investigate RT1 class II gene polymorphisms using molecular methods.
    • To differentiate diabetes-prone BB rats from non-diabetes-prone BBN rats at the genetic level.

    Main Methods:

    • Restriction fragment length polymorphism (RFLP) analysis using BamH1 and EcoR1 endonucleases.
    • Hybridization with an I-A alpha (class II mouse MHC) gene probe.

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  • Study of RT1 class II gene polymorphisms in BB and BBN rats.

    • Main Results:

    • Four polymorphic chromosome types (la, lb, lla, llb) were identified in BBN rats.
    • All diabetes-prone BB rats were homozygous for the lla/lla genotype.
    • This genetic difference was observed despite serological indistinguishability (RT1u).

    Conclusions:

    • The BB rat's RT1-linked diabetogenic gene (RT1-DM) is hypothesized to be linked to an I-A alpha-defined gene on the lla chromosome.
    • The ability to distinguish RT1u haplotypes in BB rats is a significant advancement.
    • This genetic characterization provides a tool for localizing and understanding RT1-DM.