Progressive skeletal muscle weakness in transgenic mice expressing CTG expansions is associated with the activation of the ubiquitin–proteasome pathway-

Authors
A. Vignaud, A. Ferry, A. Huguet, M. Baraibar, C. Trollet et al.

Lab
Université Pierre et Marie Curie, Paris, France.

Journal
Neuromuscular Disorders

Abstract
Myotonic dystrophy type 1 (DM1) is a neuromuscular disease caused by the expansion of a CTG repeat in the DMPK gene and characterised by progressive skeletalmuscleweakness and wasting. To investigate the effects of the CTGexpansion on the physiological function of the skeletalmuscles, we have used a transgenicmouse model carrying the human DM1 region with 550 expanded CTG repeats. Maximal force is reduced in the skeletalmuscles of 10-month-old but not in 3-month-old DM1 mice when compared to age-matched non-transgenic littermates. The progressive weakness observed in the DM1 mice is directly related to the reduced muscle mass and muscle fibre size. A significant increase in trypsin-like proteasome activity and Fbxo32 expression is also measured in the DM1 muscles indicating that an atrophic process mediated by the ubiquitin–proteasomepathway may contribute to the progressive muscle wasting and weakness in the DM1 mice.

BIOSEB Instruments Used:
Grip strength test (BIO-GS3)