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

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• 作者：Alban Vignaud ; Arnaud Ferry ; Aline Huguet ; Martin Baraibar ; Capucine Trollet ; Janek Hyzewicz ; Gillian Butler-Browne ; Jack Puymirat ; Genevieve Gourdon ; Denis Furling
• 关键词：CTG repeat ; Transgenic mouse ; DMPK gene ; Myotonic dystrophy
• 刊名：Neuromuscular Disorders
• 出版年：2010
• 出版时间：May 2010
• 年：2010
• 卷：20
• 期：5
• 页码：319-325
• 全文大小：706 K

文摘

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 skeletal muscle weakness and wasting. To investigate the effects of the CTG expansion on the physiological function of the skeletal muscles, we have used a transgenic mouse model carrying the human DM1 region with 550 expanded CTG repeats. Maximal force is reduced in the skeletal muscles 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–proteasome pathway may contribute to the progressive muscle wasting and weakness in the DM1 mice.