
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.
Mice, Knockout, Heterozygote, Tumor Suppressor Proteins, Neuropeptides, Gene Expression Regulation, Developmental, Embryo, Mammalian, Tuberous Sclerosis Complex 1 Protein, Rats, EMC ONWAR-01-94-01, Mice, Animals, Ras Homolog Enriched in Brain Protein, EMC MGC-02-96-01, Cells, Cultured, EMC COEUR-09, Monomeric GTP-Binding Proteins
Mice, Knockout, Heterozygote, Tumor Suppressor Proteins, Neuropeptides, Gene Expression Regulation, Developmental, Embryo, Mammalian, Tuberous Sclerosis Complex 1 Protein, Rats, EMC ONWAR-01-94-01, Mice, Animals, Ras Homolog Enriched in Brain Protein, EMC MGC-02-96-01, Cells, Cultured, EMC COEUR-09, Monomeric GTP-Binding Proteins
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