Transgenic mouse model for myotonic dystrophy: dmsxl carrying >1000 ctg repeats

This transgenic mice model ("DMSXL") contains large human genomic DNA sequence carrying the DMPK gene with very large repeat (>1200 CTG). They show intergenerational and somatic instability biased towards expansions. Homozygous mice, expressing enough toxic RNA carrying CUG expansion display a clear phenotype and some DM1 features: Growth retardation, muscle weakness, myotonia, splicing defects in muscle heart and brain, especially at young ages. Brain, muscles and heart abnormalities are under characterisation.

Interest / Relevance: These mice are used to study the molecular and patho-physiological consequences of CTG expansions. They are also used for gene therapy experiments and pharmacological preclinical studies. Because the DMPK transgene is expressed under the control of its own promoter and in various tissues (as in human), they can be used for systemic preclinical experiments.

Keywords: mice model, myotonic dystrophy type 1, DM1

Publications:

Seznec H Agbulut O Savouret C Sergeant N Ghestem A Tabti N Willer JC Ourth L Duros C Brisson E Fouquet C Buttler-Browne G Delacourte A Junien C and Gourdon G. (2001) Mice transgenic for the human myotonic dystrophy region with expanded CTG repeats display muscular and brain abnormalities. Human Molecular Genetics 200110 :2717-2726.

07-2 Gomes-Pereira M Foiry L Nicole A Huguet A Junien C Munnich A and Gourdon G. CTG trinucleotide repeat ?big jumps?: large expansions small mice. PloS Genetics 2007 6;3(4):epub52

Reference:

RT00399