Genetic analysis of α₄ 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 α₄ 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 α₄ subunit and used them to generate chimeric mice. These chimeric mice showed high contributions of α₄-null cells in many tissues, including skeletal muscle, and muscles lacking any detectable (<2%) α₄-positive cells did not reveal any gross morphological abnormalities. Furthermore, assays for in vitro myogenesis using either pure cultures of α₄-null myoblasts derived from the chimeras or α₄-null ES cells showed conclusively that α₄ integrins are not essential for muscle cell fusion and differentiation. Taking these results together, we conclude that α₄ integrins appear not to play essential roles in normal skeletal muscle development.