Studies on the genes of the major histocompatibility locus (RLA) of the rabbit have revealed major differences in the organization of these genes compared to other species. Molecular analyses of genes in the rabbit MHC (RLA) by pulsed field gel electrophoresis have shown that the relative order of class II genes (DP, DO, DQ, DR) is identical to that in humans and similar to that in mouse. However, a major difference from either HLA or H-2 was observed at the DR end of the RLA class II complex: class I genes are located in close proximity to DR with no interposed class III sequences. A further unique feature was found by comparison of two different RLA haplotypes, A and B. Mapping data indicated that the distance between the DQ and DR subregions differs by approximately 700 kb in the two haplotypes and this difference segregates within rabbit population. The large genetically determined difference presumably derives from an insertion/deletion even in different haplotypes. The RLA complex includes a class II beta chain similar to human MHC-DOB which has a conserved structure and expression pattern different from other class II genes. the rabbit DOB gene was obtained from a rabbit spleen cDNA library and the deduced amino acid sequence showed the typical structure of a class II beta chain; comparisons revealed that the rabbit DOB is closely related to HLA-DOB and to H-2 I-Abeta2, having 74% amino acid identity to HLA-DOB and 67% to the mouse gene product. Restriction fragment length polymorphism analysis of the rabbit DOB gene showed extensive polymorphism compared to that seen for the human HLA-DOB. However, sequence analyses of DOB from different rabbit MHC haplotypes indicated that exon 2 of the DOB gene, which encodes the beta1 domain, is highly conserved in all haplotypes tested. This finding, along with that of the insertion/deletion between DOB and DPA1 in different rabbit MHC haplotypes, suggest that RFLP patterns reflect structural differences in sequences flanking the DOB gene. A search for the functional role for DOB in underway.
