Growth retardation and increased apoptosis in mice with homozygous disruption of the <i>akt1</i> gene

TLDR

The serine/threonine kinase Akt is known to regulate cell survival and metabolism. The study disrupts the ubiquitously expressed akt1 gene in mice to investigate its role. Akt1‑/‑ mice are viable but smaller, have a shortened lifespan under genotoxic stress, do not develop diabetes, and show increased spontaneous apoptosis in testes and thymus, impaired spermatogenesis, heightened sensitivity of thymocytes to γ‑irradiation and dexamethasone, and greater susceptibility of MEFs to TNF, anti‑Fas, UV irradiation, and serum withdrawal.

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 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 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.