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

Alban Vignaud; Arnaud Ferry; Aline Huguet; Martin Baraibar; Capucine Trollet; Janek Hyzewicz; Gillian Butler-Browne; Jack Puymirat; Genevieve Gourdon; Denis Furling

doi:10.1016/j.nmd.2010.03.006

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

Neuromuscul Disord. 2010 May;20(5):319-25. doi: 10.1016/j.nmd.2010.03.006. Epub 2010 Mar 25.

Authors

Alban Vignaud¹, Arnaud Ferry, Aline Huguet, Martin Baraibar, Capucine Trollet, Janek Hyzewicz, Gillian Butler-Browne, Jack Puymirat, Genevieve Gourdon, Denis Furling

Affiliation

¹ Université Pierre et Marie Curie-Paris6, UMRS974, F-75013 Paris, France.

PMID: 20346670
DOI: 10.1016/j.nmd.2010.03.006

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 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Animals
Disease Models, Animal
Disease Progression
Hand Strength / physiology
Humans
Laminin / metabolism
Mice
Mice, Transgenic
Muscle Proteins / metabolism
Muscle Strength / genetics
Muscle Weakness / genetics
Muscle Weakness / physiopathology*
Muscle, Skeletal / physiopathology*
Myosin Heavy Chains / genetics
Myosin Heavy Chains / metabolism
Myotonic Dystrophy / genetics
Myotonic Dystrophy / pathology*
Myotonin-Protein Kinase
Proteasome Endopeptidase Complex / metabolism*
Protein Serine-Threonine Kinases / genetics*
SKP Cullin F-Box Protein Ligases / metabolism
Signal Transduction / genetics
Statistics, Nonparametric
Trinucleotide Repeat Expansion / genetics*
Ubiquitin / metabolism*

Substances

DMPK protein, human
DMPK protein, mouse
Laminin
Muscle Proteins
Ubiquitin
Fbxo32 protein, mouse
SKP Cullin F-Box Protein Ligases
Myotonin-Protein Kinase
Protein Serine-Threonine Kinases
Proteasome Endopeptidase Complex
Myosin Heavy Chains