Rheb Is Essential for Murine Development
Copyright policy )Rheb Is Essential for Murine Development
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.
- Erasmus University Rotterdam Netherlands
- Erasmus University Medical Center Netherlands
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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