Yang J T, Rando T A, Mohler W A, Rayburn H, Blau H M, Hynes R O
Howard Hughes Medical Institute. Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
J Cell Biol. 1996 Nov;135(3):829-35. doi: 10.1083/jcb.135.3.829.
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.
基于体内免疫定位研究和体外抗体阻断实验，有人提出与血管细胞黏附分子1（VCAM-1）相互作用的α4整合素参与了肌发生和骨骼肌发育。为了验证这一观点，我们构建了编码α4亚基的基因纯合缺失的胚胎干细胞（ES细胞），并用它们来培育嵌合体小鼠。这些嵌合体小鼠在包括骨骼肌在内的许多组织中显示出α4缺失细胞的高嵌合率，并且缺乏任何可检测到的（<2%）α4阳性细胞的肌肉并未显示出任何明显的形态异常。此外，使用源自嵌合体的α4缺失成肌细胞的纯培养物或α4缺失ES细胞进行的体外肌发生分析最终表明，α4整合素对于肌肉细胞融合和分化并非必不可少。综合这些结果，我们得出结论，α4整合素似乎在正常骨骼肌发育中不发挥关键作用。
