Related Experiment Video
Updated: Aug 23, 2026
Derivation of Stem Cell Lines from Mouse Preimplantation Embryos
Published on: August 20, 2017
mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells
Mirei Murakami1, Tomoko Ichisaka, Mitsuyo Maeda
1Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Nara 630-0192, Japan.
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.
Insights
Mammalian target of rapamycin (mTOR) is crucial for early mouse embryo development. Disrupting mTOR kinase activity in mice leads to embryonic lethality due to impaired cell proliferation and size control.
Area of Science:
- Cell Biology
- Developmental Biology
- Biochemistry
Background:
- The target of rapamycin (TOR) pathway regulates cell growth and is conserved across eukaryotes.
- While TOR's role in yeast and flies is known, its in vivo function in mammals is unclear.
- Previous studies suggest TOR signaling impacts cell size and proliferation.
Purpose of the Study:
- To investigate the in vivo function of mammalian target of rapamycin (mTOR) in early mouse development.
- To determine the role of mTOR kinase activity in embryonic cell proliferation and size control.
Main Methods:
- Homologous recombination was used to disrupt the kinase domain of mouse mTOR.
- Homozygous and heterozygous mutant mice were generated and analyzed.
- Mouse embryonic stem cells and blastocysts were cultured in vitro to assess proliferation and cell size.
Main Results:
- Homozygous mTOR mutant embryos exhibited embryonic lethality shortly after implantation.
- Impaired cell proliferation was observed in both embryonic and extraembryonic tissues of homozygous mutants.
- Deletion of essential C-terminal amino acids crucial for mTOR kinase activity resulted in reduced cell size and proliferation arrest in embryonic stem cells.
Conclusions:
- Mammalian target of rapamycin (mTOR) is essential for controlling cell size and proliferation in early mouse embryos.
- mTOR kinase activity is critical for post-implantation embryonic development and the viability of embryonic stem cells.
