Redundancy of myostatin and growth/differentiation factor 11 function

被引:128
作者
McPherron, Alexandra C. [1 ]
Huynh, Thanh V. [2 ]
Lee, Se-Jin [2 ]
机构
[1] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA
[2] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA
基金
美国国家卫生研究院;
关键词
BONE-MORPHOGENETIC PROTEIN; SKELETAL-MUSCLE MASS; BETA SUPERFAMILY; NEGATIVE REGULATOR; SIGNALING PATHWAY; AXIAL SKELETON; GROWTH; FOLLISTATIN; ACTIVIN; GDF11;
D O I
10.1186/1471-213X-9-24
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Myostatin (Mstn) and growth/differentiation factor 11 (Gdf11) are highly related transforming growth factor beta (TGF beta) family members that play important roles in regulating embryonic development and adult tissue homeostasis. Despite their high degree of sequence identity, targeted mutations in these genes result in non- overlapping phenotypes affecting distinct biological processes. Loss of Mstn in mice causes a doubling of skeletal muscle mass while loss of Gdf11 in mice causes dramatic anterior homeotic transformations of the axial skeleton, kidney agenesis, and an increase in progenitor cell number in several tissues. In order to investigate the possible functional redundancy of myostatin and Gdf11, we analyzed the effect of eliminating the functions of both of these signaling molecules. Results: We show that Mstn(-/-) Gdf11(-/-) mice have more extensive homeotic transformations of the axial skeleton than Gdf11(-/-) mice in addition to skeletal defects not seen in single mutants such as extra forelimbs. We also show that deletion of Gdf11 specifically in skeletal muscle in either Mstn(+/+) or Mstn(-/-) mice does not affect muscle size, fiber number, or fiber type. Conclusion: These results provide evidence that myostatin and Gdf11 have redundant functions in regulating skeletal patterning in mice but most likely not in regulating muscle size.
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页数:9
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