Open AccessSox6 is a candidate gene for p 100H myopathy, heart block, and sudden neonatal death
Author(s) -
Nobuko Hagiwara,
Scott E. Klewer,
Ricardo A. Samson,
Drew T. Erickson,
Mary F. Lyon,
Murray H. Brilliant
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.97.8.4180
Subject(s) - locus (genetics) , biology , mutant , allele , skeletal muscle , myopathy , genetics , cardiac muscle , gene , microbiology and biotechnology , endocrinology
The mousep locus encodes a gene that functions in normal pigmentation. We have characterized a radiation-induced mutant allele of the mousep locus that is associated with a failure-to-thrive syndrome, in addition to diminished pigmentation. Mice homozygous for this mutant allele,p 100H , show delayed growth and die within 2 wk after birth. We have discovered that the mutant mice develop progressive atrioventricular heart block and significant ultrastructural changes in both cardiac and skeletal muscle cells. These observations are common characteristics described in human myopathies. The karyotype ofp 100H chromosomes indicated that the mutation is associated with a chromosome 7 inversion. We demonstrate here that thep 100H chromosomal inversion disrupts both thep gene and theSox6 gene. NormalSox6 gene expression has been examined by Northern blot analysis and was found most abundantly expressed in skeletal muscle in adult mouse tissues, suggesting an involvement ofSox6 in muscle maintenance. Thep 100H mutant is thus a useful animal model in the elucidation of myopathies at the molecular level.