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

被引:336
作者
Shiota, Chiyo
Woo, Jeong-Taek
Lindner, Jill
Shelton, Kathy D.
Magnuson, Mark A.
机构
[1] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Sch Med, Ctr Stem Cell Biol, Nashville, TN 37232 USA
关键词
D O I
10.1016/j.devcel.2006.08.013
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The rapamycin-insensitive mTOR complex 2 (mTORC2) has been suggested to play an important role in growth factor-de pendent 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.
引用
收藏
页码:583 / 589
页数:7
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