title: Cardiomyopathy in the dystrophin/utrophin-deficient mouse model of severe muscular dystrophy is characterized by dysregulation of matrix metalloproteinases.
abstract: 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.
authors: Department of Molecular and Cellular Biochemistry, The Ohio State University, College of Medicine, Columbus, OH 43210, United States.
authors: Dawn A
authors: DA
authors: Delfín
authors: Kara E
authors: KE
authors: Zang
authors: Kevin E
authors: KE
authors: Schill
authors: Nikita T
authors: NT
authors: Patel
authors: Paul M L
authors: PM
authors: Janssen
authors: Subha V
authors: SV
authors: Raman
authors: Jill A
authors: JA
authors: Rafael-Fortney
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D016189:Dystrophin / Q000172:deficiency; D005260:Female; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D049411:Utrophin / Q000172:deficiency / Q000378:metabolism
chemical_list: D016189:Dystrophin; D049411:Utrophin; D020782:Matrix Metalloproteinases