GENETIC-MAPPING NEAR THE MYD LOCUS ON MOUSE CHROMOSOME-8

Myodystrophy (myd), an autosomal recessive mutation of the mouse chara cterized by progressive weakness and dystrophic muscle histology, maps to the central portion of Chromosome (Chr) 8 (Lane et al. J. Hered 67 , 135, 1976). This portion of Chr 8 contains the genes for a mitochond rial uncoupling protein (Ucp) and kallikrein (Kal3), which map to dist al 4q in the human, providing evidence for a segment of homology. Char acteristics of the myd phenotype coupled with this homology suggest th at myd may be a mouse homolog of facioscapulohumeral muscular dystroph y (FSHD), which maps to human 4q35. We have confirmed and expanded the region of mouse 8-human 4 homology by generating a map of Chr 8 in an interspecific backcross of C57BL/6J and a partially inbred strain der ived from M. spretus. The map is comprised of the genes for Ucp, coagu lation factor XI (CSII), and chloride channel 5 (Clc5), all of which h ave homologs on distal human 4q, 15 microsatellite loci, and the membr ane cofactor protein pseudogene (Mcp-ps). To place myd in the genetic map, 75 affected progeny from an intersubspecific backcross of animals heterozygous for myd with Mus musculus castaneus were genotyped with Chr 8 microsatellite loci. The mutation maps between D8Mit30 and D8Mit 75, an interval that is flanked by genes with human homologs at distal 4q. These results are consistent with the possibility that myd is the mouse homolog of FSHD.