Physical mapping of the MHC and grc by pulse field electrophoresis

The development of the physical map of the major histocompatibility complex of the rat was undertaken using pulse field gel electrophoresis of fragments of genomic DNA from the BIL/2 (grc+) and BIL/1 (grc-) strains obtained primarily from single and double digests with the enzymes Mlu I, Not I, and Sfi I and hybridized with a variety of mouse, rat, and human probes. Both strains are maintained by inbreeding the BIL heterozygote (forced heterozygosity; F31); hence, their differences lie almost entirely in the MHC-grc regions. The MHC-grc region was contained in five fragments of DNA comprising 3000-3200 kilobases (kb); thus, its size appears to be closer to that of the human MHC than to that of the mouse MHC. This distance may be an underestimate of the size of the entire region, however, because the cluster of class I loci in the RT1. A region could not be defined in detail in this study. The most striking difference between the BIL/2 strain, which has normal growth and reproductive characteristics, and the BIL/1 strain, which has growth and reproductive defects and an enhanced susceptibility to chemical carcinogens, is a deletion of approximately 70 kb in the latter strain. The studies on grc+ and grc- strains suggest that the phenotypic defects of the grc- strains may be due to the loss of genes that are normally present in this deleted region.