Essential role of protein kinase Bγ (PKBγ/Akt3) in postnatal brain development but not in glucose homeostasis

Tschopp, Oliver; Yang, Zhong; Brodbeck, Daniela; Dümmler, Bettina; Hemmings‐Mieszczak, Maja; Watanabe, Takashi; Michaelis, Thomas; Frahm, Jens; Hemmings, Brian A.

doi:10.1242/dev.01864

Cited by 364 publications

(362 citation statements)

References 68 publications

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“…This was recently confirmed by muscle-specific overexpression of constitutively active Akt2 in mice [11]. Finally, Akt3 plays a role in the development and organisation of the nervous system [12,13]. Partially overlapping functions of the Akt isoforms have, however, been suggested by recent reports showing that Akt1, in addition to Akt2, plays a role in insulin action in adipocytes [14] and in lipid metabolism in skeletal muscle cells [15].…”

Section: Introductionmentioning

confidence: 87%

Isoform-specific defects of insulin stimulation of Akt/protein kinase B (PKB) in skeletal muscle cells from type 2 diabetic patients

et al. 2008

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Section: Introductionmentioning

confidence: 87%

Isoform-specific defects of insulin stimulation of Akt/protein kinase B (PKB) in skeletal muscle cells from type 2 diabetic patients

et al. 2008

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“…216 The brains of these animals also have smaller ventricles and thinner white matter tracts connecting the corpus callosum. 217 In mouse models of tuberous sclerosis, the conditional loss of Tsc1 leads to abnormal dendritic spine morphology and density, 218 enhanced cortical excitability, 219 enlarged neurons in the cortex and hippocampus, and seizures. 220 The altered excitation state of cortex in the Tsc1 conditional null mouse is not associated with tuber formation or changes in distribution of GAD67, used as a marker for GABAergic function.…”

Section: The Conditional Pten-null Mousementioning

confidence: 99%

Advances in behavioral genetics: mouse models of autism

2007

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Autism is a neurodevelopmental syndrome with markedly high heritability. The diagnostic indicators of autism are core behavioral symptoms, rather than definitive neuropathological markers. Etiology is thought to involve complex, multigenic interactions and possible environmental contributions. In this review, we focus on genetic pathways with multiple members represented in autism candidate gene lists. Many of these pathways can also be impinged upon by environmental risk factors associated with the disorder. The mouse model system provides a method to experimentally manipulate candidate genes for autism susceptibility, and to use environmental challenges to drive aberrant gene expression and cell pathology early in development. Mouse models for fragile X syndrome, Rett syndrome and other disorders associated with autistic-like behavior have elucidated neuropathology that might underlie the autism phenotype, including abnormalities in synaptic plasticity. Mouse models have also been used to investigate the effects of alterations in signaling pathways on neuronal migration, neurotransmission and brain anatomy, relevant to findings in autistic populations. Advances have included the evaluation of mouse models with behavioral assays designed to reflect disease symptoms, including impaired social interaction, communication deficits and repetitive behaviors, and the symptom onset during the neonatal period. Research focusing on the effect of gene-by-gene interactions or genetic susceptibility to detrimental environmental challenges may further understanding of the complex etiology for autism.

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“…Akt2 has been shown to be present in intestinal cells (35), although it is expressed mainly in insulin-responsive organs, including liver, skeletal muscle, and adipose tissue, and functions primarily in insulin signaling (8,11,18,23). Akt3 is expressed abundantly in the brain and testis, and mice lacking Akt3 have smaller brains (19,57). While Akt activation is involved in the regulation of apoptosis in normal intestinal epithelial cells (65), the Salmonella-induced activation of Akt has been shown to protect epithelial cells from apoptosis (32).…”

mentioning

confidence: 99%

Protective Role of Akt2 in Salmonella enterica Serovar Typhimurium-Induced Gastroenterocolitis

Kum

2011

Infect Immun

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The Salmonella effector protein SopB has previously been shown to induce activation of Akt and protect epithelial cells from apoptosis in vitro. To characterize the role of Akt2 in host defense against Salmonella enterica serovar Typhimurium infection, wild-type (WT) mice and mice lacking Akt2 (Akt2 knockout [KO] mice) were infected using a Salmonella acute gastroenteritis model. Infected Akt2 KO mice showed a more pronounced morbidity and mortality associated with higher bacterial loads in the intestines and elevated levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-␣), gamma interferon (IFN-␥), and MCP-1, in the colons at 1 day postinfection compared to those shown in WT mice. Histopathological assessment and immunohistochemical analysis of cecal sections at 1 day postinfection revealed more severe inflammation and higher levels of neutrophil infiltration in the ceca of Akt2 KO mice. Flow cytometry analysis further confirmed an increase in the recruitment of Gr-1 ؉ CD11b ؉ neutrophils and F4/80 ؉ CD11b ؉ macrophages in the intestines of infected Akt2 KO mice. Additionally, enhanced levels of annexin V ؉ and terminal transferase dUTP nick end labeling-positive (TUNEL ؉ ) apoptotic cells in the intestines of infected Akt2 KO mice were also observed, indicating that Akt2 plays an essential role in protection against apoptosis. Finally, the differences in bacterial loads and cecal inflammation in WT and Akt2 KO mice infected with WT Salmonella were abolished when these mice were infected with the sopB deletion mutant, indicating that SopB may play a role in protecting the mice from Salmonella infection through the activation of Akt2. These data demonstrate a definitive phenotypic abnormality in the innate response in mice lacking Akt2, underscoring the important protective role of Akt2 in Salmonella infection.

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Essential role of protein kinase Bγ (PKBγ/Akt3) in postnatal brain development but not in glucose homeostasis

Cited by 364 publications

References 68 publications

Isoform-specific defects of insulin stimulation of Akt/protein kinase B (PKB) in skeletal muscle cells from type 2 diabetic patients

Isoform-specific defects of insulin stimulation of Akt/protein kinase B (PKB) in skeletal muscle cells from type 2 diabetic patients

Advances in behavioral genetics: mouse models of autism

Protective Role of Akt2 in Salmonella enterica Serovar Typhimurium-Induced Gastroenterocolitis

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