Independent regulation of the myotonic dystrophy 1 locus genes postnatallyand during adult skeletal muscle regenerator

Myotonic dystrophy is caused by a CTG, expansion in the 5'-untranslated reg ion of a serine/threonine protein kinase gene (DMPK), which is flanked by t wo other genes, DMWD and SIX5, One hypothesis to explain the wide-ranging e ffects of this expansion is that, as the mutation expands, it alters the ex pression of one or more of these genes. The effects may vary in different t issues and developmental stages, but it has been difficult to develop these hypotheses as the normal postnatal developmental expression patterns of th ese genes have not been adequately investigated. We have developed accurate transcript quantification based on fluorescent real-time reverse transcrip tion-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 s elected 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 adu lt lens, questioning a previous model of cataractogenesis mediated solely b y effects on Six5 expression. Additionally, using an in vivo model, we have shown that Dmpk levels decrease during the early stages of muscle regenera tion, Our data provide a framework for investigation of tissue-specific pat hological mechanisms in this disorder.