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PMID: 14749366 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Expression of a mutant lamin A that causes Emery-Dreifuss muscular dystrophy inhibits in vitro differentiation of C2C12 myoblasts.

Molecular and cellular biology ·Vol. 24 ·No. 4 ·2004-02-00 ·Pages 1481-92

Favreau C, Higuet D, Courvalin JC, Buendia B

Abstract

Autosomal dominantly inherited missense mutations in lamins A and C cause several tissue-specific diseases, including Emery-Dreifuss muscular dystrophy (EDMD) and Dunnigan-type familial partial lipodystrophy (FPLD). Here we analyze myoblast-to-myotube differentiation in C2C12 clones overexpressing lamin A mutated at arginine 453 (R453W), one of the most frequent mutations in EDMD. In contrast with clones expressing wild-type lamin A, these clones differentiate poorly or not at all, do not exit the cell cycle properly, and are extensively committed to apoptosis. These disorders are correlated with low levels of expression of transcription factor myogenin and with the persistence of a large pool of hyperphosphorylated retinoblastoma protein. Since clones mutated at arginine 482 (a site responsible for FPLD) differentiate normally, we conclude that C2C12 clones expressing R453W-mutated lamin A represent a good cellular model to study the pathophysiology of EDMD. Our hypothesis is that lamin A mutated at arginine 453 fails to build a functional scaffold and/or to maintain the chromatin compartmentation required for differentiation of myoblasts into myocytes.

MeSH Terms
Animals Apoptosis Biomarkers/analysis Cell Cycle Cell Differentiation Cell Line Gene Expression Regulation, Developmental Lamin Type A/genetics,metabolism Mice Models, Biological Muscle Development Muscular Dystrophy, Emery-Dreifuss/genetics Mutation/genetics Myoblasts/cytology,metabolism Nuclear Envelope/metabolism Organ Specificity Phosphorylation Proliferating Cell Nuclear Antigen/metabolism Retinoblastoma Protein/metabolism
Chemicals
Biomarkers Lamin Type A Proliferating Cell Nuclear Antigen Retinoblastoma Protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Favreau Catherine
Département de Biologie Cellulaire, Institut Jacques Monod, CNRS, Universités Paris 6 & 7, 75251 Paris cedex 05, France.
Higuet Dominique
Courvalin Jean-Claude
Buendia Brigitte
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.4.1481-1492.2004
Published
2004-02-00
Pages
1481-92
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC344177
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.24.4.1481-1492.2004 PMC Full Text View journal details
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