ArticleHuman molecular genetics2011
A novel Akt3 mutation associated with enhanced kinase activity and seizure susceptibility in mice.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 66 citations in OpenAlex.
- The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development.Genes & diseases · 2024Review
- A Two-Hit Approach Inducing Flurothyl Seizures in Fmr1 Knockout Mice Impacts Anxiety and Repetitive Behaviors.Brain sciences · 2024Article
- The genetic basis of neurocranial size and shape across varied lab mouse populations.Journal of anatomy · 2022Article
- Research models of neurodevelopmental disorders: The right model in the right place.Frontiers in neuroscience · 2022Review
- 4E-BP2-dependent translation in parvalbumin neurons controls epileptic seizure threshold.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Roots of the Malformations of Cortical Development in the Cell Biology of Neural Progenitor Cells.Frontiers in neuroscience · 2021Review
- PIK3R2/Pik3r2 Activating Mutations Result in Brain Overgrowth and EEG Changes.Annals of neurology · 2020Article
- NR2F1 regulates regional progenitor dynamics in the mouse neocortex and cortical gyrification in BBSOAS patients.The EMBO journal · 2020Article
- Neurodegenerative pathways as targets for acquired epilepsy therapy development.Epilepsia open · 2020Review
- Waking up quiescent neural stem cells: Molecular mechanisms and implications in neurodevelopmental disorders.PLoS genetics · 2020Review
- Cortical Seizures inInternational journal of molecular sciences · 2019Article
- Mechanistic Target of Rapamycin Pathway in Epileptic Disorders.Journal of Korean Neurosurgical Society · 2019Article
- Akt3-Mediated Protection Against Inflammatory Demyelinating Disease.Frontiers in immunology · 2019Article
- Structural Analysis of Hippocampal Kinase Signal Transduction.ACS chemical neuroscience · 2018Article
- Article
- Akt3 inhibits adipogenesis and protects from diet-induced obesity via WNK1/SGK1 signaling.JCI insight · 2017Article
- Mutations of AKT3 are associated with a wide spectrum of developmental disorders including extreme megalencephaly.Brain : a journal of neurology · 2017Article
- Induction of Expansion and Folding in Human Cerebral Organoids.Cell stem cell · 2017Article
- Brain Development and Akt Signaling: the Crossroads of Signaling Pathway and Neurodevelopmental Diseases.Journal of molecular neuroscience : MN · 2017Review
- Neuroprotective Role of the PI3 Kinase/Akt Signaling Pathway in Zebrafish.Frontiers in endocrinology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
In a phenotype-driven mutagenesis screen, a novel, dominant mouse mutation, Nmf350, caused low seizure threshold, sporadic tonic-clonic seizures, brain enlargement and ectopic neurons in the dentate hilus and molecular layer of the hippocampus. Genetic mapping implicated Akt3, one of four candidates within the critical interval. Sequencing analysis revealed that mutants have a missense mutation in Akt3 (encoding one of three AKT/protein kinase B molecules), leading to a non-synonymous amino acid substitution in the highly conserved protein kinase domain. Previous knockout studies showed that Akt3 is pivotal in postnatal brain development, including a smaller brain, although seizures were not observed. In contrast to Akt3(Nmf350), we find that Akt3 null mice exhibit an elevated seizure threshold. An in vitro kinase assay revealed that Akt3(Nmf350) confers higher enzymatic activity, suggesting that Akt3(Nmf350) might enhance AKT signaling in the brain. In the dentate gyrus of Akt3(Nmf350) homozygotes, we also observed a modest increase in immunoreactivity of phosphorylated ribosomal protein S6, an AKT pathway downstream target. Together these findings suggest that Akt3(Nmf350) confers an increase of AKT3 activity in specific neuronal populations in the brain, and a unique dominant phenotype. Akt3(Nmf350) mice provide a new tool for studying physiological roles of AKT signaling in the brain, and potentially novel mechanisms for epilepsy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.