Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene.
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 more susceptible to apoptosis induced by TNF, anti-Fas, UV irradiation, and serum withdrawal.
Chen
W S
WS
Department of Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607, USA. billyschen@hotmail.com
Xu
P Z
PZ
Gottlob
K
K
Chen
M L
ML
Sokol
K
K
Shiyanova
T
T
Roninson
I
I
Weng
W
W
Suzuki
R
R
Tobe
K
K
Kadowaki
T
T
Hay
N
N
D000483:Alleles; D000818:Animals; D017209:Apoptosis; D029681:Arabidopsis Proteins; D015153:Blotting, Western; D001835:Body Weight / Q000235:genetics; D002478:Cells, Cultured; D003433:Crosses, Genetic; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D005720:Gamma Rays; D005838:Genotype; D005938:Glucocorticoids / Q000494:pharmacology; D006720:Homozygote; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010641:Phenotype; D010940:Plant Proteins / Q000235:genetics* / Q000502:physiology*; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology*; D013091:Spermatogenesis / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism; D013737:Testis / Q000473:pathology; D013950:Thymus Gland / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000378:metabolism
D029681:Arabidopsis Proteins; D016895:Culture Media, Serum-Free; D005938:Glucocorticoids; D010940:Plant Proteins; D015221:Potassium Channels; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C074500:AKT1 protein, Arabidopsis; D003907:Dexamethasone