Mechanistic Target of Rapamycin (Mtor) Is Essential for Murine Embryonic Heart Development and Growth

Yi Zhu, Karla M.P. Pires, Kevin J. Whitehead, Curtis D. Olsen, Benjamin Wayment, Yi Cheng Zhang, Heiko Bugger, Olesya Ilkun, Sheldon E. Litwin, George Thomas, Sara C. Kozma, E. Dale Abel

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


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.

Original languageEnglish (US)
Article numbere54221
JournalPloS one
Issue number1
StatePublished - Jan 14 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General


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