Activation of caspase-3 apoptotic pathways in skeletal muscle fibers in laminin alpha 2-deficient mice

dy/dy mice, which carry an unidentified mutation in the Lama2 gene, show dy strophic pathologies similar to those of human congenital muscular dystroph y. Laminin alpha 2 deficiency induces apoptosis with DNA fragmentation. Cas pases, which are involved in various types of cell death, are sequentially activated through a processing by other members of caspases. By using a cle avage site-directed antibody against caspase-3 that specifically reacts wit h the active form of caspase-3, we immunochemically demonstrated that caspa se-3 is activated in the skeletal muscle fiber of dy/dy mice and that some of the activated caspase-3 muscle fibers are TUNEL-positive. Thus the lack of laminin alpha 2 signals activates caspase-3, resulting in the apoptosis of muscle fibers. (C) 1999 Academic Press.