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

William S. Chen; Pei-Zhang Xu; Kathrin Gottlob; Mei-Ling Chen; Karen Sokol; Tanya Shiyanova; Igor B. Roninson; Wei Weng; Ryo Suzuki; Kazuyuki Tobe; Takashi Kadowaki; Nissim Hay

doi:10.1101/gad.913901

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.

Keywords

AKT1BiologyApoptosisProtein kinase BAKT2PhosphorylationMolecular biologyCancer researchEndocrinologyCell biologyInternal medicineGeneticsMedicine

MeSH Terms

AllelesAnimalsApoptosisArabidopsis ProteinsBlottingWesternBody WeightCellsCulturedCrossesGeneticCulture MediaSerum-FreeDexamethasoneDiabetes MellitusExperimentalFibroblastsGamma RaysGenotypeGlucocorticoidsHomozygoteIn Situ Nick-End LabelingMaleMiceMiceKnockoutModelsGeneticMutagenesisSite-DirectedMutationPhenotypePlant ProteinsPotassium ChannelsSpermatogenesisT-LymphocytesTestisThymus GlandTime FactorsTumor Necrosis Factor-alphafas Receptor

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Publication Info

Year: 2001
Type: article
Volume: 15
Issue: 17
Pages: 2203-2208
Citations: 919
Access: Closed

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APA Style

                            
                                
                                    William S. Chen, 
                                
                                    Pei-Zhang Xu, 
                                
                                    Kathrin Gottlob
                                
                                et al.
                            
                            (2001). 
                            Growth retardation and increased apoptosis in mice with homozygous disruption of the <i>akt1</i> gene. 
                            Genes & Development
                            , 15
                            (17)
                            , 2203-2208.
                            https://doi.org/10.1101/gad.913901
                        

Identifiers

DOI: 10.1101/gad.913901
PMID: 11544177
PMCID: PMC312770

Data Quality

Data completeness: 86%