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

doi:10.1371/journal.pone.0054221

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Mechanistic target of rapamycin (Mtor) is essential for murine embryonic heart development and growth

Journal article

Open access

Peer reviewed

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, …

PloS one, Vol.8(1), pp.e54221-e54221

2013

DOI: 10.1371/journal.pone.0054221

PMCID: PMC3544830

PMID: 23342106

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Abstract

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.

Animals

TOR Serine-Threonine Kinases - genetics

TOR Serine-Threonine Kinases - metabolism

Heart - embryology

Embryonic Development - genetics

Embryonic Development - physiology

Female

Mice

Blotting, Western

Mice, Knockout

Details

Title: Subtitle: Mechanistic target of rapamycin (Mtor) is essential for murine embryonic heart development and growth
Creators: Yi Zhu - 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
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
Resource Type: Journal article
Publication Details: PloS one, Vol.8(1), pp.e54221-e54221
DOI: 10.1371/journal.pone.0054221
PMID: 23342106
PMCID: PMC3544830
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: T32 DK091317 / NIDDK NIH HHS R01 DK092065 / NIDDK NIH HHS U54 HL112311 / NHLBI NIH HHS U01HL087947 / NHLBI NIH HHS U01 HL087947 / NHLBI NIH HHS S10 RR027506 / NCRR NIH HHS R01DK092065 / NIDDK NIH HHS
Language: English
Date published: 2013
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984025265202771

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