BAG3 deficiency results in fulminant myopathy and early lethality

S Homma, M Iwasaki, GD Shelton, E Engvall… - The American journal of …, 2006 - Elsevier
S Homma, M Iwasaki, GD Shelton, E Engvall, JC Reed, S Takayama
The American journal of pathology, 2006Elsevier
Bcl-2-associated athanogene 3 (BAG3) is a member of a conserved family of cyto-protective
proteins that bind to and regulate Hsp70 family molecular chaperones. Here, we show that
BAG3 is prominently expressed in striated muscle and colocalizes with Z-disks. Mice with
homozygous disruption of the bag3 gene developed normally but deteriorated postnatally
with stunted growth evident by 1 to 2 weeks of age and death by 4 weeks. BAG3-deficient
animals developed a fulminant myopathy characterized by noninflammatory myofibrillar …
Bcl-2-associated athanogene 3 (BAG3) is a member of a conserved family of cyto-protective proteins that bind to and regulate Hsp70 family molecular chaperones. Here, we show that BAG3 is prominently expressed in striated muscle and colocalizes with Z-disks. Mice with homozygous disruption of the bag3 gene developed normally but deteriorated postnatally with stunted growth evident by 1 to 2 weeks of age and death by 4 weeks. BAG3-deficient animals developed a fulminant myopathy characterized by noninflammatory myofibrillar degeneration with apoptotic features. Knockdown of bag3 expression in cultured C2C12 myoblasts increased apoptosis on induction of differentiation, suggesting a need for bag3 for maintenance of myotube survival and confirming a cell autonomous role for bag3 in muscle. We conclude that although BAG3 is not required for muscle development, this co-chaperone appears to be critically important for maintenance of mature skeletal muscle.
Elsevier