Sox6 is a candidate gene for p100H myopathy, heart block, and sudden neonatal death

The mouse p locus encodes a gene that functions in normal pigmentation. We have characterized a radiation-induced mutant allele of the mouse p locus t hat is associated with a failure-to-thrive syndrome, in addition to diminis hed pigmentation. Mice homozygous for this mutant allele, p(100H), show del ayed growth and die within 2 wk after birth. We have discovered that the mu tant mice develop progressive atrioventricular heart block and significant ultrastructural changes in both cardiac and skeletal muscle cells. These ob servations are common characteristics described in human myopathies, The ka ryotype of p(100H) chromosomes indicated that the mutation is associated wi th a chromosome 7 inversion. We demonstrate here that the p(100H) chromosom al inversion disrupts both the p gene and the Sox6 gene. Normal Sox6 gene e xpression has been examined by Northern blot analysis and was found most ab undantly expressed in skeletal muscle in adult mouse tissues, suggesting an involvement of Sox6 in muscle maintenance, The p(100H) mutant is thus a us eful animal model in the elucidation of myopathies at the molecular level.