Send to

Choose Destination
Neuromuscul Disord. 2012 Nov;22(11):1006-14. doi: 10.1016/j.nmd.2012.05.002. Epub 2012 Jun 29.

Cardiomyopathy in the dystrophin/utrophin-deficient mouse model of severe muscular dystrophy is characterized by dysregulation of matrix metalloproteinases.

Author information

Department of Molecular and Cellular Biochemistry, The Ohio State University, College of Medicine, Columbus, OH 43210, United States.


Cardiomyopathy is a significant component in Duchenne muscular dystrophy. Although mdx mice are deficient in dystrophin, they only develop mild indicators of cardiomyopathy before 1year-of-age, making therapeutic investigations using this model lengthy. In contrast, mdx mice also lacking utrophin (utrn(-/-);mdx) show severely reduced cardiac contractile function and histological indicators of cardiomyopathy by 8-10weeks-of-age. Here we demonstrate that utrn(-/-);mdx mice show a similar pattern of cardiac damage to that in dystrophic patients. Matrix metalloproteinases required for ventricular remodeling during the evolution of heart failure are upregulated in utrn(-/-);mdx mice concurrent with the onset of cardiac pathology by 10weeks-of-age. Matrix metalloproteinase activity is further dysregulated due to reduced levels of endogenous tissue inhibitors and co-localizes with fibroblasts and collagen I-containing scars. utrn(-/-);mdx mice are therefore a very useful model for investigating potential cardiac therapies.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center