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.

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Persistent URL dx.doi.org/10.1128/MCB.00985-10, hdl.handle.net/1765/25580
Citation
Goorden, S.M.I., Hoogeveen-Westerveld, M., Cheng, C., van Woerden, G.M., Mozaffari, E., Post, L., … Elgersma, Y.. (2011). Rheb is essential for murine development. Molecular and Cellular Biology, 31(8), 1672–1678. doi:10.1128/MCB.00985-10