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.
Genetic analysis of alpha 4 integrin functions in the development of mouse skeletal muscle.
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J T Yang, T A Rando, W A Mohler, H Rayburn, H M Blau, R O Hynes; Genetic analysis of alpha 4 integrin functions in the development of mouse skeletal muscle.. J Cell Biol 1 November 1996; 135 (3): 829–835. doi: https://doi.org/10.1083/jcb.135.3.829
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