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PMID: 15254238 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells.

Molecular and cellular biology ·Vol. 24 ·No. 15 ·2004-08-00 ·Pages 6710-8

Murakami M, Ichisaka T, Maeda M, Oshiro N, Hara K, Edenhofer F, Kiyama H, Yonezawa K, Yamanaka S

Abstract

TOR is a serine-threonine kinase that was originally identified as a target of rapamycin in Saccharomyces cerevisiae and then found to be highly conserved among eukaryotes. In Drosophila melanogaster, inactivation of TOR or its substrate, S6 kinase, results in reduced cell size and embryonic lethality, indicating a critical role for the TOR pathway in cell growth control. However, the in vivo functions of mammalian TOR (mTOR) remain unclear. In this study, we disrupted the kinase domain of mouse mTOR by homologous recombination. While heterozygous mutant mice were normal and fertile, homozygous mutant embryos died shortly after implantation due to impaired cell proliferation in both embryonic and extraembryonic compartments. Homozygous blastocysts looked normal, but their inner cell mass and trophoblast failed to proliferate in vitro. Deletion of the C-terminal six amino acids of mTOR, which are essential for kinase activity, resulted in reduced cell size and proliferation arrest in embryonic stem cells. These data show that mTOR controls both cell size and proliferation in early mouse embryos and embryonic stem cells.

MeSH Terms
Animals Blastocyst/metabolism Blotting, Southern Cell Cycle Cell Division Embryo, Mammalian/cytology Flow Cytometry Gene Deletion Genotype Heterozygote Mice Mice, Knockout Models, Genetic Mutation Protein Kinases/metabolism,physiology Protein Structure, Tertiary Recombination, Genetic Ribosomal Protein S6 Kinases/metabolism Sirolimus/pharmacology Stem Cells/metabolism,physiology TOR Serine-Threonine Kinases Time Factors Tissue Distribution
Chemicals
Protein Kinases mTOR protein, mouse Ribosomal Protein S6 Kinases TOR Serine-Threonine Kinases Sirolimus
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Murakami Mirei
Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Nara 630-0192, Japan.
Ichisaka Tomoko
Maeda Mitsuyo
Oshiro Noriko
Hara Kenta
Edenhofer Frank
Kiyama Hiroshi
Yonezawa Kazuyoshi
Yamanaka Shinya
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.15.6710-6718.2004
Published
2004-08-00
Pages
6710-8
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC444840
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.24.15.6710-6718.2004 PMC Full Text View journal details
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