Dystrophin defi ciency combined with reduced muscle stem cell res | 21252
Journal of Cell Science & Therapy

Journal of Cell Science & Therapy
Open Access

ISSN: 2157-7013

+44 1300 500008

Dystrophin defi ciency combined with reduced muscle stem cell reserve in mdx/ mTR mice models Duchenne Muscular Dystrophy

International Conference & Exhibition on Cell Science & Stem Cell Research

29 Nov - 1 Dec 2011 Philadelphia Airport Marriott, USA

Alessandra Sacco, Foteini Mourkioti, Jason Pomerantz and Helen M. Blau

Accepted Abstracts: J Cell Sci Ther

Abstract :

In Duchenne Muscular Dystrophy (DMD), dystrophin mutation leads to progressive lethal skeletal muscle degeneration. Eventually in patients functional muscle tissue is supplanted by fi brosis, calcium deposits and adipose accumulation that coincides with clinical manifestations. Although clearly initiated by dystrophin defi ciency, the pathophysiological cause of eventual failure of the tissue repair process is unknown. Unfortunately dystrophin defi ciency does not recapitulate DMD in mice (mdx), which have mild skeletal muscle defects and potent regenerative capacity. Th e absence of a mouse model for DMD that faithfully mimics key features of the human disease has limited our understanding of its pathophysiology and tests of potential therapies. We postulated that human DMD progression is a consequence of loss of muscle stem cell function and that the mild mouse mdx phenotype results from greater reserve fueled by longer telomeres. To test this hypothesis, we crossed dystrophic mdx mice with mice lacking the RNA component of the telomerase enzyme Terc. We report that this novel mouse model has severe muscular dystrophy with profound muscle weakness, elevated serum enzyme levels, and increased muscle fi brosis and calcium deposits. Th eir muscle stem cells exhibit reduced proliferative and regenerative capacity in vitro and in vivo upon transplantation and their progeny has shortened telomeres. Th ese data suggest that DMD progression results from a cell autonomous failure of muscle stem cells to maintain the damage-repair cycle initiated by dystrophin defi ciency. Th e essential role of muscle stem cell function has implications for treatment approaches for DMD.