Moderate intergenerational and somatic instability of a 55-CTG repeat in transgenic mice
| Autor: | Geneviève Gourdon, Hlène Hofmann-Radvanyi, Martine Blanche, François Radvanyi, Chantal Duros, Marc Abitbol, Claudine Junien, Anne-Sophie Lia |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Genetically modified mouse
Untranslated region Male congenital hereditary and neonatal diseases and abnormalities DNA Complementary Somatic cell Mice Transgenic Biology medicine.disease_cause Myotonic dystrophy Polymerase Chain Reaction Mice Trinucleotide Repeats Genetics medicine Animals Humans Myotonic Dystrophy Transgenes Gene Mutation Mosaicism Myotonin-protein kinase Middle Aged medicine.disease Cosmids Molecular biology Trinucleotide repeat expansion |
| Zdroj: | Nature genetics. 15(2) |
| ISSN: | 1061-4036 |
| Popis: | 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)1. The (CTG)n repeat is polymorphic and varies in size between 5 and 37 repeats in unaffected individuals1 whereas in affected patients there are between 50 and 4,000 CTGs2,3. The size of the (CTG)n.repeat, which increases through generations, generally correlates with clinical severity and age of onset4. The instability of the CTG repeat appears to depend on its size as well as on the sex of the transmitting parent5–9. Moreover, mitotic instability analysis of different human DM tissues shows length mosaicism between different cell lineages3,6,10–14. 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 instability15–17 |
| Databáze: | OpenAIRE |
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