Résumé :
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Myotonic dystrophy type 1 (DM1) is caused by the amplification of a CTG repeat and is characterized by a wide spectrum of clinical manifestations affecting skeletal muscle such as progressive weakness, wasting and myotonia. In order to investigate the role of the CTG mutation in the development of the disease, a transgenic DM1 mice, carrying the CTG expansion and producing an abnormal human DMPK with 350 repeats has been developed by Gourdon’s group. These mice reproduce some features of the human disease, such as myotonia. In the present study, we have characterized the functional properties of the skeletal muscles of these transgenic mice. A progressive decrease of force production (weakness) with age was measured in the tibialis anterior TA of the DM1 mice. This weakness is progressive and a significant 30% decrease in the force was measured in 10-month old DM1 mice. However, the ratio force/mass did not seem to be different between non-transgenic and transgenic mice, indicating that the weakness is caused by a loss in muscle mass. To determine if the muscle wasting in DM1 mice is associated with an active process, we have examined by northern blot the expression of the atrogin-1, a muscle-specific ubiquitin-ligase required for muscle atrophy. Our results showed that the expression of atrogin-1 is significantly increased in both 3- and 10-month old transgenic mice when compared to age-matched control. Its expression also increases with age confirming the progressive muscle atrophy of the DM1 mice. In conclusion this mouse model reproduces the progressive muscle atrophy that is observed in human patients and may be used to evaluate therapeutic strategies.
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