Activation of caspase 3, 9, 12, and Bax in masseter muscle of mdx mice during necrosis

J Muscle Res Cell Motil. 2007;28(4-5):243-7. doi: 10.1007/s10974-007-9122-9. Epub 2007 Oct 19.


The mdx mouse, a model of muscular dystrophy, lacks dystrophin, a cell membrane protein. It is known that the lack of dystrophin causes muscle fiber necrosis from 2 weeks after birth, and the majority of necrotic muscle fibers are replaced by regenerated muscle fibers by 4 weeks after birth. A recent study indicated the possibility that mitochondria-mediated intracellular stress, a phenomenon similar to apoptosis, may be produced during muscle fiber necrosis, but did not analyze endoplasmic reticulum-mediated intracellular stress. Therefore, we examined the expression of the caspase-12 gene involved in the endoplasmic reticulum stress pathway and the Bax, caspase-9, and caspase-3 genes involved in the mitochondrial stress pathway in the mdx masseter muscle. We found over-expression of caspase-12 in cells at 2-3 weeks after birth when muscle fiber necrosis was not prominent. This suggests that stress occurs in the endoplasmic reticulum to maintain cell morphology in the absence of dystrophin. In addition, Bax was abundantly expressed in the mdx masseter muscle at 3 weeks after birth, and the expression of caspase-9 and -3 was prominent at 3-4 weeks after birth when necrosis and regeneration were marked. These results indicate that endoplasmic reticulum and mitochondrial stresses are produced during necrosis of the mdx masseter muscle, and suggest that these events are a phenomenon similar to apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Caspases / metabolism*
  • Dystrophin / genetics
  • Endoplasmic Reticulum / enzymology
  • Enzyme Activation / genetics
  • Genetic Predisposition to Disease / genetics
  • Male
  • Masseter Muscle / enzymology*
  • Masseter Muscle / pathology
  • Masseter Muscle / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred mdx
  • Mitochondria / enzymology
  • Muscle Fibers, Skeletal / enzymology*
  • Muscle Fibers, Skeletal / pathology
  • Muscular Dystrophy, Animal / enzymology*
  • Muscular Dystrophy, Animal / genetics
  • Muscular Dystrophy, Animal / physiopathology*
  • Necrosis / enzymology
  • Necrosis / genetics
  • Necrosis / physiopathology
  • Stress, Physiological / enzymology
  • Stress, Physiological / genetics
  • Stress, Physiological / physiopathology
  • bcl-2-Associated X Protein / metabolism*


  • Bax protein, mouse
  • Dystrophin
  • bcl-2-Associated X Protein
  • Caspases