Rheb is essential for murine development

Mol Cell Biol. 2011 Apr;31(8):1672-8. doi: 10.1128/MCB.00985-10. Epub 2011 Feb 14.


Ras homolog enriched in brain (Rheb) couples growth factor signaling to activation of the target of rapamycin complex 1 (TORC1). To study its role in mammals, we generated a Rheb knockout mouse. In contrast to mTOR or regulatory-associated protein of mTOR (Raptor) mutants, the inner cell mass of Rheb(-/-) embryos differentiated normally. Nevertheless, Rheb(-/-) embryos died around midgestation, most likely due to impaired development of the cardiovascular system. Rheb(-/-) embryonic fibroblasts showed decreased TORC1 activity, were smaller, and showed impaired proliferation. Rheb heterozygosity extended the life span of tuberous sclerosis complex 1-deficient (Tsc1(-/-)) embryos, indicating that there is a genetic interaction between the Tsc1 and Rheb genes in mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Embryo, Mammalian / metabolism
  • Gene Expression Regulation, Developmental*
  • Heterozygote
  • Mice
  • Mice, Knockout
  • Monomeric GTP-Binding Proteins / deficiency
  • Monomeric GTP-Binding Proteins / metabolism*
  • Neuropeptides / deficiency
  • Neuropeptides / metabolism*
  • Ras Homolog Enriched in Brain Protein
  • Rats
  • Tuberous Sclerosis Complex 1 Protein
  • Tumor Suppressor Proteins / deficiency
  • Tumor Suppressor Proteins / metabolism


  • Neuropeptides
  • Ras Homolog Enriched in Brain Protein
  • Rheb protein, mouse
  • Tsc1 protein, mouse
  • Tsc1 protein, rat
  • Tuberous Sclerosis Complex 1 Protein
  • Tumor Suppressor Proteins
  • Monomeric GTP-Binding Proteins