Independent regulation of the myotonic dystrophy 1 locus genes postnatally and during adult skeletal muscle regeneration.

Myotonic dystrophy is caused by a CTG(n) expansion in the 3'-untranslated region of a serine/threonine protein kinase gene (DMPK), which is flanked by two other genes, DMWD and SIX5. One hypothesis to explain the wide-ranging effects of this expansion is that, as the mutation expands, it alters the expression of one or more of these genes. The effects may vary in different tissues and developmental stages, but it has been difficult to develop these hypotheses as the normal postnatal developmental expression patterns of these genes have not been adequately investigated. We have developed accurate transcript quantification based on fluorescent real-time reverse transcription-polymerase chain reaction (TaqMan) to develop gene expression profiles during postnatal development in C57Bl/10 mice. Our results show extensive independent postnatal regulation of the myotonic dystrophy-locus genes in selected tissues and demonstrate which are the most highly expressed of the genes in each tissue. All three genes at the locus are expressed in the adult lens, questioning a previous model of cataractogenesis mediated solely by effects on Six5 expression. Additionally, using an in vivo model, we have shown that Dmpk levels decrease during the early stages of muscle regeneration. Our data provide a framework for investigation of tissue-specific pathological mechanisms in this disorder.