TY - JOUR
T1 - Requirement for serum response factor for skeletal muscle growth and maturation revealed by tissue-specific gene deletion in mice
AU - Li, Shijie
AU - Czubryt, Michael P.
AU - McAnally, John
AU - Bassel-Duby, Rhonda
AU - Richardson, James A.
AU - Wiebel, Franziska F.
AU - Nordheim, Alfred
AU - Olson, Eric N.
PY - 2005/1/25
Y1 - 2005/1/25
N2 - Serum response factor (SRF) controls the transcription of muscle genes by recruiting a variety of partner proteins, including members of the myocardin family of transcriptional coactivators. Mice lacking SRF fail to form mesoderm and die before gastrulation, precluding an analysis of the roles of SRF in muscle tissues. To investigate the functions of SRF in skeletal muscle development, we conditionally deleted the Srf gene in mice by skeletal muscle-specific expression of Cre recombinase. In mice lacking skeletal muscle SRF expression, muscle fibers formed, but failed to undergo hypertrophic growth after birth. Consequently, mutant mice died during the perinatal period from severe skeletal muscle hypoplasia. The myopathic phenotype of these mutant mice resembled that of mice expressing a dominant negative mutant of a myocardin family member in skeletal muscle. These findings reveal an essential role for the partnership of SRF and myocardin-related transcription factors in the control of skeletal muscle growth and maturation in vivo.
AB - Serum response factor (SRF) controls the transcription of muscle genes by recruiting a variety of partner proteins, including members of the myocardin family of transcriptional coactivators. Mice lacking SRF fail to form mesoderm and die before gastrulation, precluding an analysis of the roles of SRF in muscle tissues. To investigate the functions of SRF in skeletal muscle development, we conditionally deleted the Srf gene in mice by skeletal muscle-specific expression of Cre recombinase. In mice lacking skeletal muscle SRF expression, muscle fibers formed, but failed to undergo hypertrophic growth after birth. Consequently, mutant mice died during the perinatal period from severe skeletal muscle hypoplasia. The myopathic phenotype of these mutant mice resembled that of mice expressing a dominant negative mutant of a myocardin family member in skeletal muscle. These findings reveal an essential role for the partnership of SRF and myocardin-related transcription factors in the control of skeletal muscle growth and maturation in vivo.
KW - Hypertrophy
KW - Myocardin-related transcription factor
KW - Myofiber
KW - Myopathy
UR - http://www.scopus.com/inward/record.url?scp=12844273481&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12844273481&partnerID=8YFLogxK
U2 - 10.1073/pnas.0409103102
DO - 10.1073/pnas.0409103102
M3 - Article
C2 - 15647354
AN - SCOPUS:12844273481
SN - 0027-8424
VL - 102
SP - 1082
EP - 1087
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 4
ER -