Integrins play key roles in the pathogenesis of muscular dystrophies. Integrins can compensate for defects of the dystrophin-dystroglycan complex, and mutations in integrins cause certain forms of muscular dystrophy. The pathways by which integrins carry out these functions are not understood. Integrin Linked Kinase (ILK) is important for muscle function in invertebrates and was shown to be involved in muscle differentiation. Its expression is increased following muscle injury with cardiotoxin. We would like to test the hypothesis that ILK is important for muscle function, and in particular, that it plays a role in recovery of muscle following injury. We will use a genetic approach to create mice with ILK deletion in skeletal muscle. Mutant myoblasts and muscle tissue will be examined for defects in proliferation, differentiation, adhesion and survival. The role of ILK as a cytoskeletal adaptor and as a kinase in muscle will be addressed. Two murine injury models, cardiotoxin injection and dystrophin/ILK double mutants, will be used to test the role of ILK in muscle regeneration. These studies will lead to a better understanding of integrin signaling in muscle and define the pathways that may eventually serve as targets for muscular dystrophy therapy. ? ?
| Niewmierzycka, Agnieszka; Mills, Julia; St-Arnaud, Rene et al. (2005) Integrin-linked kinase deletion from mouse cortex results in cortical lamination defects resembling cobblestone lissencephaly. J Neurosci 25:7022-31 |
