Growth retardation and increased apoptosis in mice with homozygous disruption of the akt1 gene

被引：787

作者：

Chen, WS ^{[1
]}

Xu, PZ

Gottlob, K

Chen, ML

Sokol, K

Shiyanova, T

Roninson, I

Weng, W

Suzuki, R

Tobe, K

Kadowaki, T

Hay, N

机构：

[1] Univ Illinois, Coll Med, Dept Mol Genet, Chicago, IL 60607 USA

[2] Univ Illinois, Res Resources Ctr, Chicago, IL 60612 USA

[3] Rockefeller Univ, New York, NY 10021 USA

[4] Ingenious Targeting Lab, Stony Brook, NY 11790 USA

[5] Univ Tokyo, Dept Metab Dis, Tokyo 1138655, Japan

来源：

GENES & DEVELOPMENT | 2001年 / 15卷 / 17期

关键词：

gamma irradiation; glucose tolerance; seminiferous tubular atrophy; thymocytes; mouse embryo fibroblasts;

D O I：

10.1101/gad.913901

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The serine/threonine kinase Akt has been implicated in the control of cell survival and metabolism. Here we report the disruption of the most ubiquitously expressed member of the akt family of genes, akt1, in the mouse. Akt1(-/-) mice are viable but smaller when compared to wild-type littermates. In addition, the life span of Akt1(-/-) mice, upon exposure to genotoxic stress, is shorter. However, Akt1(-/-) mice do not display a diabetic phenotype. Increased spontaneous apoptosis in testes, and attenuation of spermatogenesis is observed in Akt1(-/-) male mice. Increased spontaneous apoptosis is also observed in the thymi of Akt1(-/-) mice, and Akt1(-/-)thymocytes are more sensitive to apoptosis induced by gamma -irradiation and dexamethasone. Finally, Akt1(-/-)mouse embryo fibroblasts (MEFs) are mote susceptible to apoptosis induced by TNF, anti-Fas, UV irradiation, and serum withdrawal.

引用

页码：2203 / 2208

页数：6

共 39 条

[31] PIK3CA is implicated as an oncogene in ovarian cancer [J].

Shayesteh, L ;

Lu, YL ;

Kuo, WL ;

Baldocchi, R ;

Godfrey, T ;

Collins, C ;

Pinkel, D ;

Powell, B ;

Mills, GB ;

Gray, JW .

NATURE GENETICS, 1999, 21 (01) :99-102

[32] PTEN: Life as a tumor suppressor [J].

Simpson, L ;

Parsons, R .

EXPERIMENTAL CELL RESEARCH, 2001, 264 (01) :29-41

[33] MOLECULAR-CLONING OF THE AKT ONCOGENE AND ITS HUMAN HOMOLOGS AKT1 AND AKT2 - AMPLIFICATION OF AKT1 IN A PRIMARY HUMAN GASTRIC ADENOCARCINOMA [J].

STAAL, SP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (14) :5034-5037

[34] Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN [J].

Stambolic, V ;

Suzuki, A ;

de la Pompa, JL ;

Brothers, GM ;

Mirtsos, C ;

Sasaki, T ;

Ruland, J ;

Penninger, JM ;

Siderovski, DP ;

Mak, TW .

CELL, 1998, 95 (01) :29-39

[35] AGE-RELATED HISTOLOGIC-CHANGES IN THE ADULT-MOUSE TESTIS [J].

TAKANO, H ;

ABE, K .

ARCHIVUM HISTOLOGICUM JAPONICUM, 1987, 50 (05) :533-544

[36] INSULIN-RESISTANCE AND GROWTH-RETARDATION IN MICE LACKING INSULIN-RECEPTOR SUBSTRATE-1 [J].

TAMEMOTO, H ;

KADOWAKI, T ;

TOBE, K ;

YAGI, T ;

SAKURA, H ;

HAYAKAWA, T ;

TERAUCHI, Y ;

UEKI, K ;

KABURAGI, Y ;

SATOH, S ;

SEKIHARA, H ;

YOSHIOKA, S ;

HORIKOSHI, H ;

FURUTA, Y ;

IKAWA, Y ;

KASUGA, M ;

YAZAKI, Y ;

AIZAWA, S .

NATURE, 1994, 372 (6502) :182-186

[37] Potential role of protein kinase B in glucose transporter 4 translocation in adipocytes [J].

Tanti, JF ;

Grillo, S ;

Gremeaux, T ;

Coffer, PJ ;

VanObberghen, E ;

LeMarchandBrustel, Y .

ENDOCRINOLOGY, 1997, 138 (05) :2005-2010

[38] NEONATAL LETHALITY AND LYMPHOPENIA IN MICE WITH A HOMOZYGOUS DISRUPTION OF THE C-ABL PROTOONCOGENE [J].

TYBULEWICZ, VLJ ;

CRAWFORD, CE ;

JACKSON, PK ;

BRONSON, RT ;

MULLIGAN, RC .

CELL, 1991, 65 (07) :1153-1163

[39] Cell-autonomous regulation of cell and organ growth in Drosophila by Akt/PKB [J].

Verdu, J ;

Buratovich, MA ;

Wilder, EL ;

Birnbaum, MJ .

NATURE CELL BIOLOGY, 1999, 1 (08) :500-506

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