TY - JOUR
T1 - Redundancy of myostatin and growth/differentiation factor 11 function
AU - McPherron, Alexandra C.
AU - Huynh, Thanh V.
AU - Lee, Se Jin
N1 - Funding Information:
We thank N. Brockoff and J. Portas for assistance in maintenance of mouse lines, B. Sauer for the Cre vector, S. Pearson-White for the MDAF2 vector, and the Johns Hopkins Transgenic Core Facility for carrying out the pronuclear and blastocyst injections. This work was supported by grants from the National Institutes of Health (R01HD35887 and U54AR052646, to S-J.L.) and the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, USA (A.C.M.).
PY - 2009
Y1 - 2009
N2 - Abstract. Background. Myostatin (Mstn) and growth/differentiation factor 11 (Gdf11) are highly related transforming growth factor (TGF) 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.
AB - Abstract. Background. Myostatin (Mstn) and growth/differentiation factor 11 (Gdf11) are highly related transforming growth factor (TGF) 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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U2 - 10.1186/1471-213X-9-24
DO - 10.1186/1471-213X-9-24
M3 - Article
C2 - 19298661
AN - SCOPUS:64249143104
VL - 9
JO - BMC Developmental Biology
JF - BMC Developmental Biology
SN - 1471-213X
IS - 1
M1 - 24
ER -