We are conducting studies of genes of the rabbit immune system by techniques of molecular biology. We have demonstrated evolutionary conservation of both sequence and linkage relationships of gene segments encoding T cell receptor Beta chain variable regions. Three VBeta genes, each represented as only a single copy in the haploid genome of the rabbit was found on a 4,290 bp genomic DNA fragment. They do not appear to have classical upstream promoter sequences but all three are found expressed as mature size mRNA transcripts. The linked rabbit VBeta are remarkably different from each other and are more similar to human and mouse VBeta than to each other. This suggests that the genes duplicated early, prior to rabbit-mouse radiation. We have discovered restriction fragment length polymorphism (RFLP) of the rabbit T cell receptor Beta chain constant region genes as well as probable allotypic forms. We are using the RFLP and allotypes to study whether rabbit CBeta and CKappa are genetically linked as they are in mice, or unlinked as in man. A germline VBeta gene with homology to mouse VBeta 86T1 had a DNA sequence identical to that of the VBeta portion of a cDNA from a second rabbit suggesting that the expressed gene had not undergone any somatic mutations. Like other species, rabbits have two similar CBeta genes but we have now shown that some rabbits appear to have allotypic forms of CBeta1 and three different CBeta. Some CBeta allotypic differences are found at amino acid positions where analogous CKappa allotypic differences occur.
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