Rheb Is Essential for Murine Development

被引：63

作者：

Goorden, Susanna M. I. ^{[1
]}

Hoogeveen-Westerveld, Marianne ^{[2
]}

Cheng, Caroline ^{[3
]}

van Woerden, Geeske M. ^{[1
]}

Mozaffari, Melika ^{[1
]}

Post, Laura ^{[1
]}

Duckers, Henricus J. ^{[3
]}

Nellist, Mark ^{[2
]}

Elgersma, Ype ^{[1
]}

机构：

[1] Erasmus MC, Univ Med Ctr, Dept Neurosci, NL-3000 CA Rotterdam, Netherlands

[2] Erasmus MC, Univ Med Ctr, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands

[3] Erasmus MC, Univ Med Ctr, Dept Expt Cardiol, Mol Cardiol Lab,Thoraxctr, NL-3000 CA Rotterdam, Netherlands

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2011年 / 31卷 / 08期

关键词：

TUBEROUS SCLEROSIS GENE; CELL-GROWTH; MOUSE MODEL; MTOR; LETHALITY; PROTEINS; GTPASE; TSC1; MICE; IDENTIFICATION;

D O I：

10.1128/MCB.00985-10

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1672 / 1678

页数：7

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