title: Rheb is essential for murine development.
abstract: 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.
authors.affiliation: Department of Neuroscience, Erasmus MC University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, Netherlands.
authors.forename: Susanna M I
authors.initials: SM
authors.lastname: Goorden
authors.forename: Marianne
authors.initials: M
authors.lastname: Hoogeveen-Westerveld
authors.forename: Caroline
authors.initials: C
authors.lastname: Cheng
authors.forename: Geeske M
authors.initials: GM
authors.lastname: van Woerden
authors.forename: Melika
authors.initials: M
authors.lastname: Mozaffari
authors.forename: Laura
authors.initials: L
authors.lastname: Post
authors.forename: Henricus J
authors.initials: HJ
authors.lastname: Duckers
authors.forename: Mark
authors.initials: M
authors.lastname: Nellist
authors.forename: Ype
authors.initials: Y
authors.lastname: Elgersma
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D020559:Monomeric GTP-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D009479:Neuropeptides / Q000172:deficiency / Q000378:metabolism*; D000076205:Ras Homolog Enriched in Brain Protein; D051381:Rats; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000378:metabolism
chemical_list: D009479:Neuropeptides; D000076205:Ras Homolog Enriched in Brain Protein; C490213:Rheb protein, mouse; C000624651:Tsc1 protein, mouse; C000624652:Tsc1 protein, rat; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D020559:Monomeric GTP-Binding Proteins