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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Moderate intergenerational and somatic instability of a 55-CTG repeat in transgenic mice.

Myotonic dystrophy ( DM) is associated with the expansion of a (CTG)n trinucleotide repeat in the 3' untranslated region (UTR) of the DM protein kinase gene (DMPK). The (CTG)n repeat is polymorphic and varies in size between 5 and 37 repeats in unaffected individuals whereas in affected patients there are between 50 and 4,000 CTGs. The size of the (CTG)n repeat, which increases through generations, generally correlates with clinical severity and age of onset. The instability of the CTG repeat appears to depend on its size as well as on the sex of the transmitting parent. Moreover, mitotic instability analysis of different human DM tissues shows length mosaicism between different cell lineages. The molecular mechanisms of triplet instability remain elusive. To investigate the role of genomic sequences in instability, we produced transgenic mice containing a 45-kb genomic segment with a 55-CTG repeat cloned from a mildly affected patient. In contrast to other mouse models containing CAG repeats within cDNAs, these mice showed both intergenerational and somatic repeat instability.[1]


  1. Moderate intergenerational and somatic instability of a 55-CTG repeat in transgenic mice. Gourdon, G., Radvanyi, F., Lia, A.S., Duros, C., Blanche, M., Abitbol, M., Junien, C., Hofmann-Radvanyi, H. Nat. Genet. (1997) [Pubmed]
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