Calpain-6 Deficiency Promotes Skeletal Muscle Development and Regeneration

• DOI: 10.1371/journal.pgen.1003668
• Publication Date: 2013-08-01T20:45:11Z
• Authors: Kazuo Tonami; Shoji Hata; Koichi Ojima; Yasuko Ono; Yukiko Kurihara; Tomokazu Amano; Takahiro Sato; Yumiko Kawamura; Hiroki Kurihara; Hiroyuki Sorimachi
• Keywords: 0303 health sciences; Calpain; Embryonic Development; Gene Expression Regulation, Developmental; Cell Differentiation; QH426-470; Muscle Development; Microtubules; Mice; 03 medical and health sciences; Genetics; Animals; Humans; Regeneration; Muscle, Skeletal; Research Article

Calpains are Ca2+-dependent modulator Cys proteases that have a variety of functions in almost all eukaryotes. There more than 10 well-conserved mammalian calpains, among which eutherian calpain-6 (CAPN6) is unique it has amino acid substitutions at the active-site residue (to Lys humans), strongly suggesting loss proteolytic activity. CAPN6 expressed predominantly embryonic muscles, placenta, and several cultured cell lines. We previously reported involved regulating microtubule dynamics actin reorganization cells. The physiological CAPN6, however, still unclear. Here, to elucidate CAPN6's vivo roles, we generated Capn6-deficient mice, lacZ expression cassette was integrated into Capn6 gene. These mouse embryos skeletal as well cartilage heart. Histological biochemical analyses showed deficiency promoted development muscle. In primary muscle cells were induced differentiate myotubes, detected myocytes, cultures increased differentiation. Furthermore, found regenerating muscles adult mice after cardiotoxin-induced degeneration. this experimental system, exhibited advanced skeletal-muscle regeneration heterozygotes or wild-type same time point. results collectively promotes differentiation during both regeneration, novel function suppressor