Mechanistic target of rapamycin (Mtor) is essential for murine embryonic heart development and growth.
Mechanistic target of rapamycin (Mtor) is required for embryonic inner cell mass proliferation during early development. However, Mtor expression levels are very low in the mouse heart during embryogenesis. To determine if Mtor plays a role during mouse cardiac development, cardiomyocyte specific Mtor deletion was achieved using α myosin heavy chain (α-MHC) driven Cre recombinase. Initial mosaic expression of Cre between embryonic day (E) 10.5 and E11.5 eliminated a subset of cardiomyocytes with high Cre activity by apoptosis and reduced overall cardiac proliferative capacity. The remaining cardiomyocytes proliferated and expanded normally. However loss of 50% of cardiomyocytes defined a threshold that impairs the ability of the embryonic heart to sustain the embryo's circulatory requirements. As a result 92% of embryos with cardiomyocyte Mtor deficiency died by the end of gestation. Thus Mtor is required for survival and proliferation of cardiomyocytes in the developing heart.
Division of Endocrinology, Metabolism, and Diabetes and Program in Molecular Medicine, School of Medicine, University of Utah, Salt Lake City, Utah, United States of America.
Yi
Y
Zhu
Karla M P
KM
Pires
Kevin J
KJ
Whitehead
Curtis D
CD
Olsen
Benjamin
B
Wayment
Yi Cheng
YC
Zhang
Heiko
H
Bugger
Olesya
O
Ilkun
Sheldon E
SE
Litwin
George
G
Thomas
Sara C
SC
Kozma
E Dale
ED
Abel
D000818:Animals; D015153:Blotting, Western; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D006321:Heart / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D058570:TOR Serine-Threonine Kinases