DR. LOUIS KUNKEL, BOSTON CHILDREN’S HOSPITAL

The Zebrafish (Danio rerio) is an excellent animal model for the study of genetic disorders due to its biological similarity to humans, advanced molecular genetics, small size, permeability to small molecules and rapid development. The fish are ideal for studying processes that are difficult or impossible to follow in other animals. Our lab has successfully used zebrafish to model dystrophin deficiency (sapje) and to screen small molecules from drug libraries previously approved for use in humans. These studies have led us to the identification of compounds that partially correct for dystrophin deficiency. Unfortunately, chemical screenings for other progressive muscular dystrophies have yet to be done. It is our goal to use a zebrafish model for calpainopathy to test small molecules; but first we need to create a calpain-3 knockout model in zebrafish. To do this, we propose to use transcription activator-like nucleases (TALENs), an effective reverse genetic tool for the targeted knockout of specific genes. We will study the knockout fish to further understand the pathogenesis of the disease and eventually use it as a model for pre-clinical studies, including drug screening.

C3 organized and hosted the first U.S. scientific conference focused solely on LGMD2A: "Clinical Characteristics and Pathogenic Mechanisms of LGMD2A/calpainopathy". On October 27, 2011, twenty-four esteemed scientists from eight countries attended the workshop. A book containing abstracts submitted by the presenters is available here. The second global conference organized by C3 is slated for November 2013.

C3 sponsored "2012 New Directions in Biology and Disease of Skeletal Muscle Conference", which highlighted current developments in muscle biology, disease, and therapy with presentations by leading international researchers. More information is available here.

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C3KO mouse expression analysis: downregulation of the muscular dystrophy Ky protein and alterations in muscle aging, click here

Calpain 3, the Gatekeeper of Proper Assembly, Turnover and Maintenance, click here

Molecular and Cellular Basis of Calpainopathy, click here

Slug is a Novel Downstream Target of MyoD, click here

For a review of calpainopathy sponsored by GeneReviews
click here

For a review of calpainopathy sponsored the National Center for Biotechnology Information,
click here