Sox6 is a candidate gene for p(100H) myopathy, heart block, and sudden neonatal death

Nobuko Hagiwara, Scott E. Klewer, Ricardo A. Samson, Drew T. Erickson, Mary F. Lyon, Murray H. Brilliant

Research output: Contribution to journalArticle

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Abstract

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 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 of p(100H) chromosomes indicated that the mutation is associated with a chromosome 7 inversion. We demonstrate here that the p(100H) chromosomal inversion disrupts both the p gene and the Sox6 gene. Normal Sox6 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 of Sox6 in muscle maintenance. The p(100H) mutant is thus a useful animal model in the elucidation of myopathies at the molecular level.

Original languageEnglish (US)
Pages (from-to)4180-4185
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number8
DOIs
StatePublished - Apr 11 2000
Externally publishedYes

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Heart Block
Muscular Diseases
Sudden Death
Genes
Pigmentation
Skeletal Muscle
Alleles
Failure to Thrive
Chromosomes, Human, Pair 7
Atrioventricular Block
Karyotype
Cardiac Myocytes
Northern Blotting
Animal Models
Chromosomes
Maintenance
Perinatal Death
Parturition
Radiation
Gene Expression

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Sox6 is a candidate gene for p(100H) myopathy, heart block, and sudden neonatal death. / Hagiwara, Nobuko; Klewer, Scott E.; Samson, Ricardo A.; Erickson, Drew T.; Lyon, Mary F.; Brilliant, Murray H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 8, 11.04.2000, p. 4180-4185.

Research output: Contribution to journalArticle

Hagiwara, Nobuko ; Klewer, Scott E. ; Samson, Ricardo A. ; Erickson, Drew T. ; Lyon, Mary F. ; Brilliant, Murray H. / Sox6 is a candidate gene for p(100H) myopathy, heart block, and sudden neonatal death. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 8. pp. 4180-4185.
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AU - Klewer, Scott E.

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AU - Lyon, Mary F.

AU - Brilliant, Murray H.

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