Rheb Is Essential for Murine Development

Susanna Goorden; Marianne Hoogeveen - Westerveld; Caroline Cheng; Geeske van Woerden; M Mozaffari; Laura Post; Eric Duckers; Mark Nellist; Ype Elgersma

doi:10.1128/MCB.00985-10

Rheb Is Essential for Murine Development

Susanna Goorden, Marianne Hoogeveen - Westerveld, Caroline Cheng, Geeske van Woerden, M Mozaffari, Laura Post, Eric Duckers, Mark Nellist, Ype Elgersma

Research output: Contribution to journal › Article › Academic › peer-review

67 Citations (Scopus)

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.

Original language	Undefined/Unknown
Pages (from-to)	1672-1678
Number of pages	7
Journal	Molecular and Cellular Biology
Volume	31
Issue number	8
DOIs	https://doi.org/10.1128/MCB.00985-10
Publication status	Published - 2011

Research programs

EMC COEUR-09
EMC MGC-02-96-01
EMC ONWAR-01-94-01

Access to Document

10.1128/MCB.00985-10

http://hdl.handle.net/1765/25580

Cite this

@article{dd3dda2db22849d19e4b0bcba8940081,

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.",

author = "Susanna Goorden and {Hoogeveen - Westerveld}, Marianne and Caroline Cheng and {van Woerden}, Geeske and M Mozaffari and Laura Post and Eric Duckers and Mark Nellist and Ype Elgersma",

year = "2011",

doi = "10.1128/MCB.00985-10",

language = "Undefined/Unknown",

volume = "31",

pages = "1672--1678",

journal = "Molecular and Cellular Biology",

issn = "0270-7306",

publisher = "Taylor & Francis Ltd",

number = "8",

}

TY - JOUR

T1 - Rheb Is Essential for Murine Development

AU - Goorden, Susanna

AU - Hoogeveen - Westerveld, Marianne

AU - Cheng, Caroline

AU - van Woerden, Geeske

AU - Mozaffari, M

AU - Post, Laura

AU - Duckers, Eric

AU - Nellist, Mark

AU - Elgersma, Ype

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.1128/MCB.00985-10

DO - 10.1128/MCB.00985-10

M3 - Article

SN - 0270-7306

VL - 31

SP - 1672

EP - 1678

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

IS - 8

ER -