International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 189 - THE ROLE OF CALPAIN 3 IN MDM MOUSE MUSCULAR DYSTROPHY

Huebsch KA 1, Spencer MJ 2, Cox GA 1

1 The Jackson Laboratory, Bar Harbor, United States, 2 Department of Pediatrics and UCLA Duchenne Muscular Dystrophy Research Center, University of California, Los Angeles, United States

Muscular dystrophy with myositis (mdm) mice exhibit a severe and progressive muscular dystrophy with kyphosis and a rigid gait accompanied by a reduction in calpain 3 (CAPN3) levels in skeletal muscle.  The mdm mutation is a small in-frame deletion within the CAPN3 binding N2A domain of the titin gene.  We are using a genetic approach to test two alternate hypotheses regarding the role of CAPN3 in the mdm disease mechanism.  First, transgenic overexpression of CAPN3 in mdm mice will test the hypothesis that reduction of CAPN3 protein levels are critical to the disease process. Second, crosses of mdm mice with CAPN3-/- null mice will test the hypothesis that aberrant activation of CAPN3 causes the muscular dystrophy in mdm mutant mice. If CAPN3 is critical to the mdm disease process, we expect that either overexpression of CAPN3 or the complete absence of CAPN3 will alter the onset or progression of the mdm muscular dystrophy. Additionally, adding back the CAPN3 binding site in mdm mice by transgenic overexpression of the N2A domain of TTN will determine whether it can function independently to alleviate the mdm muscular dystrophy. 

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