Requirement for serum response factor for skeletal muscle growth and maturation revealed by tissue-specific gene deletion in mice
Requirement for serum response factor for skeletal muscle growth and maturation revealed by tissue-specific gene deletion in mice
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DOI：
10.1073/pnas.0409103102
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发表时间：
2005-01-25
影响因子：
11.1
通讯作者：
Olson, EN
中科院分区：
文献类型：
--
作者：
Li, SJ;Czubryt, MP;Olson, EN
血清反应因子（SRF）通过募集多种伴侣蛋白，包括转录共激活因子的心肌素家族成员，来控制肌肉基因的转录。缺乏SRF的小鼠不能形成中胚层，并在原肠胚形成前死亡，因此无法分析SRF在肌肉组织中的作用。为了研究SRF在骨骼肌发育中的功能，我们通过骨骼肌特异性表达Cre重组酶，有条件地删除了小鼠SRF基因。在缺乏骨骼肌SRF表达的小鼠中，肌肉纤维形成，但在出生后没有发生肥厚生长。结果，突变小鼠在围产期死于严重的骨骼肌发育不全。这些突变小鼠的肌病表型类似于在骨骼肌中表达心肌蛋白家族成员显性阴性突变的小鼠。这些发现揭示了SRF和心肌素相关转录因子在体内骨骼肌生长和成熟控制中的重要作用。
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.