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

被引：776
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
收藏
页码：2203 / 2208
页数：6
相关论文
共 39 条
  • [1] Mechanism of activation and function of protein kinase B
    Alessi, DR
    Cohen, P
    [J]. CURRENT OPINION IN GENETICS & DEVELOPMENT, 1998, 8 (01) : 55 - 62
  • [2] Akt2 mRNA is highly expressed in embryonic brown fat and the AKT2 kinase is activated by insulin
    Altomare, DA
    Lyons, GE
    Mitsuuchi, Y
    Cheng, JQ
    Testa, JR
    [J]. ONCOGENE, 1998, 16 (18) : 2407 - 2411
  • [3] ALTOMARE DA, 1995, ONCOGENE, V11, P1055
  • [4] Regulation of GLUT1 gene transcription by the serine threonine kinase Akt1
    Barthel, A
    Okino, ST
    Liao, JF
    Nakatani, K
    Li, JP
    Whitlock, JP
    Roth, RA
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (29) : 20281 - 20286
  • [5] Kit/stem cell factor receptor-induced activation of phosphatidylinositol 3′-kinase is essential for male fertility
    Blume-Jensen, P
    Jiang, GQ
    Hyman, R
    Lee, KF
    O'Gorman, S
    Hunter, T
    [J]. NATURE GENETICS, 2000, 24 (02) : 157 - 162
  • [6] DISRUPTION OF THE HNF-4 GENE, EXPRESSED IN VISCERAL ENDODERM, LEADS TO CELL-DEATH IN EMBRYONIC ECTODERM AND IMPAIRED GASTRULATION OF MOUSE EMBRYOS
    CHEN, WS
    MANOVA, K
    WEINSTEIN, DC
    DUNCAN, SA
    PLUMP, AS
    PREZIOSO, VR
    BACHVAROVA, RF
    DARNELL, JE
    [J]. GENES & DEVELOPMENT, 1994, 8 (20) : 2466 - 2477
  • [7] Amplification of AKT2 in human pancreatic cancer cells and inhibition of ATK2 expression and tumorigenicity by antisense RNA
    Cheng, JQ
    Ruggeri, B
    Klein, WM
    Sonoda, G
    Altomare, DA
    Watson, DK
    Testa, JR
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (08) : 3636 - 3641
  • [8] Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKBβ)
    Cho, H
    Mu, J
    Kim, JK
    Thorvaldsen, JL
    Chu, QW
    Crenshaw, EB
    Kaestner, KH
    Bartolomei, MS
    Shulman, GI
    Birnbaum, MJ
    [J]. SCIENCE, 2001, 292 (5522) : 1728 - 1731
  • [9] THYMOCYTE APOPTOSIS INDUCED BY P53-DEPENDENT AND INDEPENDENT PATHWAYS
    CLARKE, AR
    PURDIE, CA
    HARRISON, DJ
    MORRIS, RG
    BIRD, CC
    HOOPER, ML
    WYLLIE, AH
    [J]. NATURE, 1993, 362 (6423) : 849 - 852
  • [10] Coffer PJ, 1998, BIOCHEM J, V335, P1
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