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

被引:53
作者
Yang, JT
Rando, TA
Mohler, WA
Rayburn, H
Blau, HM
Hynes, RO
机构
[1] MIT,CTR CANC RES,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139
[2] MIT,DEPT BIOL,CAMBRIDGE,MA 02139
[3] STANFORD UNIV,SCH MED,DEPT MOL PHARMACOL,STANFORD,CA 94305
关键词
D O I
10.1083/jcb.135.3.829
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:829 / 835
页数:7
相关论文
共 34 条
[1]   Differential requirements for alpha 4 integrins during fetal and adult hematopoiesis [J].
Arroyo, AG ;
Yang, JT ;
Rayburn, H ;
Hynes, RO .
CELL, 1996, 85 (07) :997-1008
[2]   ALPHA-4-BETA-7-INTEGRIN MEDIATES LYMPHOCYTE BINDING TO THE MUCOSAL VASCULAR ADDRESSIN MADCAM-1 [J].
BERLIN, C ;
BERG, EL ;
BRISKIN, MJ ;
ANDREW, DP ;
KILSHAW, PJ ;
HOLZMANN, B ;
WEISSMAN, IL ;
HAMANN, A ;
BUTCHER, EC .
CELL, 1993, 74 (01) :185-195
[3]  
Bradley A., 1987, TERATOCARCINOMAS EMB, P113
[4]  
CHAN BMC, 1992, J BIOL CHEM, V267, P8366
[5]   GENOMIC SEQUENCING [J].
CHURCH, GM ;
GILBERT, W .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (07) :1991-1995
[6]   M-CADHERIN LOCALIZATION IN DEVELOPING ADULT AND REGENERATING MOUSE SKELETAL-MUSCLE - POSSIBLE INVOLVEMENT IN SECONDARY MYOGENESIS [J].
CIFUENTESDIAZ, C ;
NICOLET, M ;
ALAMEDDINE, H ;
GOUDOU, D ;
DEHAUPAS, M ;
RIEGER, F ;
MEGE, RM .
MECHANISMS OF DEVELOPMENT, 1995, 50 (01) :85-97
[7]  
DOETSCHMAN TC, 1985, J EMBRYOL EXP MORPH, V87, P27
[8]   CONSEQUENCES OF LACK OF BETA-1 INTEGRIN GENE-EXPRESSION IN MICE [J].
FASSLER, R ;
MEYER, M .
GENES & DEVELOPMENT, 1995, 9 (15) :1896-1908
[9]  
GEORGE EL, 1994, METHOD ENZYMOL, V245, P386
[10]  
GEORGE EL, 1993, DEVELOPMENT, V119, P1079