title: Development and characterization of NEX- Pten, a novel forebrain excitatory neuron-specific knockout mouse.
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 identified molecular defects resulting from Pten deletion that likely affect several aspects of neuronal development and excitability.
authors.affiliation: Department of Cell Biology and Neuroscience, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Kazdoba
authors.forename: C Nicole
authors.initials: CN
authors.lastname: Sunnen
authors.forename: Beth
authors.initials: B
authors.lastname: Crowell
authors.forename: Gum Hwa
authors.initials: GH
authors.lastname: Lee
authors.forename: Anne E
authors.initials: AE
authors.lastname: Anderson
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Arcangelo
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics / Q000378:metabolism; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism*
chemical_list: D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse