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.
Howard Hughes Medical Institute. Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
J T
JT
Yang
T A
TA
Rando
W A
WA
Mohler
H
H
Rayburn
H M
HM
Blau
R O
RO
Hynes
D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002459:Cell Fusion; D002478:Cells, Cultured; D002678:Chimera; D039441:Integrin alpha4; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000737:chemistry / Q000166:cytology / Q000254:growth & development*; D009206:Myocardium / Q000737:chemistry; D013234:Stem Cells
D015703:Antigens, CD; D039441:Integrin alpha4