Growth retardation and increased apoptosis in mice with homozygous disruption of the akt1 gene
- William S. Chen1,6,
- Pei-Zhang Xu1,
- Kathrin Gottlob1,
- Mei-Ling Chen2,
- Karen Sokol3,
- Tanya Shiyanova1,
- Igor Roninson1,
- Wei Weng4,
- Ryo Suzuki5,
- Kazuyuki Tobe5,
- Takashi Kadowaki5, and
- Nissim Hay1,6
- 1Department of Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607, USA; 2Research Resources Center, University of Illinois at Chicago, Chicago, Illinois 60612, USA; 3The Rockefeller University, New York, New York 10021, USA; 4Ingenious Targeting Laboratory, Stony Brook, New York 11790, USA; 5Department of Metabolic Diseases, University of Tokyo, 113-8655 Tokyo, Japan
Abstract
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 theakt 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 γ-irradiation and dexamethasone. Finally, Akt1−/− mouse embryo fibroblasts (MEFs) are more susceptible to apoptosis induced by TNF, anti-Fas, UV irradiation, and serum withdrawal.
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Footnotes
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↵6 Corresponding authors.
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E-MAIL nhay{at}uic.edu; FAX (312) 355-2032.
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E-MAIL billyschen{at}hotmail.com.
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Article and publication are at www.genesdev.org/cgi/doi/10.1101/gad.913901.
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- Received May 23, 2001.
- Accepted July 3, 2001.
- Cold Spring Harbor Laboratory Press
