BAG3 Deficiency Results in Fulminant Myopathy and Early Lethality

摘要: Bcl-2-associated athanogene 3 (BAG3) is a member of conserved family cyto-protective proteins that bind to and regulate Hsp70 molecular chaperones. Here, we show BAG3 prominently expressed in striated muscle colocalizes with Z-disks. Mice homozygous disruption the bag3 gene developed normally but deteriorated postnatally stunted growth evident by 1 2 weeks age death 4 weeks. BAG3-deficient animals fulminant myopathy characterized noninflammatory myofibrillar degeneration apoptotic features. Knockdown expression cultured C2C12 myoblasts increased apoptosis on induction differentiation, suggesting need for maintenance myotube survival confirming cell autonomous role muscle. We conclude although not required development, this co-chaperone appears be critically important mature skeletal