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

Dev Cell. 2006 Oct;11(4):583-9. doi: 10.1016/j.devcel.2006.08.013. Epub 2006 Sep 7.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Alleles*
  • Animals
  • Carrier Proteins / metabolism*
  • Cell Proliferation
  • Cells, Cultured
  • Embryo, Mammalian / cytology
  • Fetal Development / genetics*
  • Fetal Viability / genetics*
  • Fibroblasts / metabolism
  • Fibroblasts / physiology
  • Gene Targeting
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Protein Kinases / analysis
  • Protein Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rapamycin-Insensitive Companion of mTOR Protein
  • TOR Serine-Threonine Kinases

Substances

  • Actins
  • Carrier Proteins
  • RICTOR protein, human
  • Rapamycin-Insensitive Companion of mTOR Protein
  • rictor protein, mouse
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Proto-Oncogene Proteins c-akt

Associated data

  • GENBANK/AY540053