Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene.

By William S. Chen, Pei-Zhang Xu, Kathrin Gottlob, M. Chen, K. Sokol, Tanya Shiyanova, I. Roninson, W. Weng, R. Suzuki, K. Tobe and 2 more. Genes & Development, 2001

1,011 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/76970225f91305ebc01f1d62c382d53d0d5c9f7f

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Citations in the corpus

• Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models (2011, background): “Akt1 null Viable but shorter life span Mild growth retardation (weight 80% of control) [74, 75 ]”
• Deregulated Akt3 Activity Promotes Development of Malignant Melanoma (2004, background): “Knockout mice lacking Akt1 are growth retarded and have increased rates of spontaneous apoptosis in the testis and thymus (15, 17, 18).”
• Role for Akt3/Protein Kinase Bγ in Attainment of Normal Brain Size (2005, background): “Akt1-deficient mice display impaired overall growth, whereas Akt2 null mice are insulin intolerant, demonstrating a diabetes-like syndrome (13, 16, 17).”
• Signalling pathways that mediate skeletal muscle hypertrophy and atrophy (2003, background): “Mice that lack Akt1 are smaller than control littermates, supporting a role for Akt1 in cell growt”
• PI3K/Akt: getting it right matters (2008, background): “…mice with specific phenotypes: Akt1( / ) mice show placental hypotrophy, accompanied by retardation of growth and reduction of body weight (Chen et al., 2001; Cho et al., 2001b); Akt2( / ) mice become hyperinsulemic and hyperglycemic (Cho et al., 2001a); and Akt3( / ) mice exhibit reduced…”
• PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. (2007, result): “Taken together with results from Akt knockout mice, it is intriguing to suggest that PHLPP1 plays a role in glucose homeostasis (where Akt2 is critical) whereas PHLPP2 plays a role in cell survival (where Akt1 is critical) (Chen et al., 2001).”
• Proliferation, survival and metabolism: the role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination (2016, background): “Germline deletion of any of the isoforms alone does not lead to clear embryonic lethality despite the various physiological and pathological defects that these mice exhibit (Chen et al., 2001; Cho et al., 2001; Tschopp et al., 2005).”
• Regulation of cardiac hypertrophy by intracellular signalling pathways (2006, background): “Akt1 -null mice have a 20% reduction in body size, with a concomitant reduction in heart size, whereas Akt2 -null mice do not show any reductions in body growt”
• Mutant PIK3CA promotes cell growth and invasion of human cancer cells. (2005, background): “, 2004), that cells from AKT1 knockout mice are susceptible to serum withdrawal induced apoptosis (Chen et al., 2001), and that AKT1 is essential Figure 7.”
• Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta. (2003, background): “Both Akt1-null and Akt2-null mice are viable, but Akt1-deficient mice exhibit a growth deficiency and normal glucose metabolism (23, 24), whereas Akt2-deficient mice exhibit insulin resistance and mild diabetes with no apparent difference in size (25).”
• Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. (2006, background): “Three Akt/PKB genes with redundant functions exist in mammals (Akt1/PKBa, Akt2/ PKBb, and Akt3/PKBg), and genetic disruption of any one Akt/PKB gene results in viable animals (Chen et al., 2001; Cho et al., 2001; Easton et al., 2005; Garofalo et al., 2003).”