Development and characterization of NEX- Pten, a novel forebrain excitatory neuron-specific knockout mouse.

Developmental Neuroscience
Tatiana M KazdobaGabriella D'Arcangelo

Abstract

The phosphatase and tensin homolog located on chromosome 10 (PTEN) suppresses the activity of the phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway, a signaling cascade critically involved in the regulation of cell proliferation and growth. Human patients carrying germ line PTEN mutations have an increased predisposition to tumors, and also display a variety of neurological symptoms and increased risk of epilepsy and autism, implicating PTEN in neuronal development and function. Consistently, loss of Pten in mouse neural cells results in ataxia, seizures, cognitive abnormalities, increased soma size and synaptic abnormalities. To better understand how Pten regulates the excitability of principal forebrain neurons, a factor that is likely to be altered in cognitive disorders, epilepsy and autism, we generated a novel conditional knockout mouse line (NEX-Pten) in which Cre, under the control of the NEX promoter, drives the deletion of Pten specifically in early postmitotic, excitatory neurons of the developing forebrain. Homozygous mutant mice exhibited a massive enlargement of the forebrain, and died shortly after birth due to excessive mTOR activation. Analysis of the neonatal cerebral cortex further id...Continue Reading

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Citations

Jul 1, 2015·Journal of Neurotrauma·Ina NikolaevaGabriella D'Arcangelo
Apr 29, 2015·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Amanda K TilotCharis Eng
May 27, 2014·Frontiers in Molecular Neuroscience·Biliana O Veleva-Rotse, Anthony P Barnes
May 6, 2014·Frontiers in Molecular Neuroscience·Joaquin N LugoObi Okonkwo
May 26, 2016·Autism Research : Official Journal of the International Society for Autism Research·Amy E Clipperton-AllenDamon T Page
May 13, 2014·Cell Transplantation·Wise Young
Feb 7, 2020·Epilepsy & Behavior : E&B·Lin ZhuQian Wu
Jun 3, 2020·Molecular and Cellular Neurosciences·Yves Jossin

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