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Dev Cell. 2006 Oct;11(4):583-9. Epub 2006 Sep 7.

Multiallelic disruption of the rictor gene in mice reveals that mTOR complex 2 is essential for fetal growth and viability.

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1
Department of Molecular Physiology and Biophysics and Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.

Abstract

The rapamycin-insensitive mTOR complex 2 (mTORC2) has been suggested to play an important role in growth factor-dependent signaling. To explore this possibility further in a mammalian model system, we disrupted the expression of rictor, a specific component of mTORC2, in mice by using a multiallelic gene targeting strategy. Embryos that lack rictor develop normally until E9.5, and then exhibit growth arrest and die by E11.5. Although placental defects occur in null embryos, an epiblast-specific knockout of rictor only delayed lethality by a few days, thereby suggesting other important roles for this complex in the embryo proper. Analyses of rictor null embryos and fibroblasts indicate that mTORC2 is a primary kinase for Ser473 of Akt/PKB. Rictor null fibroblasts exhibit low proliferation rates, impaired Akt/PKB activity, and diminished metabolic activity. Taken together, these findings indicate that both rictor and mTORC2 are essential for the development of both embryonic and extraembryonic tissues.

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PMID:
16962829
DOI:
10.1016/j.devcel.2006.08.013
[Indexed for MEDLINE]
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