Genetic analysis of alpha(4) integrin functions in the development of mouse skeletal muscle

It has been suggested, on the basis of immunolocalization studies in vivo and antibody blocking experiments in vitro, that alpha(4) integrins interacting with vascular cell adhesion molecule 1 (VCAM-1) are involved in myogenesis and skeletal muscle development. To test this proposal, we generated embryonic stem (ES) cells homozygous null for the gene encoding the alpha(4) subunit and used them to generate chimeric mice. These chimeric mice showed high contributions of alpha(4)-null cells in many tissues, including skeletal muscle, and muscles lacking any detectable (<2%) alpha(4)-positive cells did not reveal any gross morphological abnormalities. Furthermore, assays for in vitro myogenesis using either pure cultures of alpha(4)-null myoblasts derived from the chimeras or alpha(4)-null ES cells showed conclusively that alpha(4) integrins are not essential for muscle cell fusion and differentiation. Taking these results together, we conclude that alpha(4) integrins appear not to play essential roles in normal skeletal muscle development.