A deletion in a rat major histocompatibility complex class I gene is linked to the absence of β2-microglobulin-containing serum molecules

Class I major histocompatibility antigens are composed of a heavy chain that is noncovalently associated with β2-microglobulin (β2m). Most class I molecules are membrane bound, but mouse and rat cDNA clones and genes without a functional code for the transmembrane amino acids have been identified. The membrane-associated class I molecules are important in the control of cell-mediated cytotoxicity, while the function of the soluble molecules remains unclear. Previous studies have shown that β2m circulates in rat serum in three different molecular weight classes. The first is free β2m (M(r), 12,000), the second is about M(r) 70,000, and the third is roughly M(r) 200,000. In an inbred subline of immunodeficient, diabetesprone BioBreeding rats (BioBreeding/Hagedorn), previous work detected two restriction fragment polymorphisms in class I major histocompatibility complex genes, one of them a gene deletion on a 7-kilobase BamHI fragment and the other on a 2-kilobase BamHI fragment. In these rats we have found that the third serum β2m-binding size class is absent. Analysis of F1 and F2 individuals following cross-breeding between Bio-Breeding/Hagedorn rats and genetically related (nondiabetic) control BioBreeding w-subline rats demonstrated that the large-size serum peak of β2m was associated with the presence of the class I restriction fragments