Drs. Hao and Akrami contributed equally to this work.
Muscleblind-like 2 (Mbnl2) -deficient mice as a model for myotonic dystrophy
Article first published online: 21 JAN 2008
Copyright © 2008 Wiley-Liss, Inc.
Volume 237, Issue 2, pages 403–410, February 2008
How to Cite
Hao, M., Akrami, K., Wei, K., De Diego, C., Che, N., Ku, J.-H., Tidball, J., Graves, M. C., Shieh, P. B. and Chen, F. (2008), Muscleblind-like 2 (Mbnl2) -deficient mice as a model for myotonic dystrophy. Dev. Dyn., 237: 403–410. doi: 10.1002/dvdy.21428
- Issue published online: 21 JAN 2008
- Article first published online: 21 JAN 2008
- Manuscript Accepted: 30 NOV 2007
- University of California, Los Angeles Laubisch fund
- Muscular Dystrophy Association. Grant Number: 4068
- myotonic dystrophy;
- chloride channel;
- muscular dystrophy
Myotonic dystrophy (DM), the most common adult-onset muscular dystrophy, is caused by CTG or CCTG microsatellite repeat expansions. Expanded DM mRNA microsatellite repeats are thought to accumulate in the nucleus, sequester Muscleblind proteins, and interfere with alternative mRNA splicing. Muscleblind2 (Mbnl2) is a member of the family of Muscleblind RNA binding proteins (that also include Mbnl1 and Mbnl3) that are known to bind CTG/CCTG RNA repeats. Recently, it was demonstrated that Mbnl1-deficient mice have characteristic features of human DM, including myotonia and defective chloride channel expression. Here, we demonstrate that Mbnl2-deficient mice also develop myotonia and have skeletal muscle pathology consistent with human DM. We also find defective expression and mRNA splicing of the chloride channel (Clcn1) in skeletal muscle that likely contributes to the myotonia phenotype. Our results support the hypothesis that Muscleblind proteins and specifically MBNL2 contribute to the pathogenesis of human DM. Developmental Dynamics 237:403–410, 2008. © 2008 Wiley-Liss, Inc.