Development and characterization of NEX- Pten, a novel forebrain excitatory neuron-specific knockout mouse.
Development and characterization of NEX- Pten, a novel forebrain excitatory neuron-specific knockout mouse.
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DOI:
10.1159/000337229
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发表时间:
2012
影响因子:
2.9
通讯作者:
D'Arcangelo G
中科院分区:
文献类型:
--
作者:
Kazdoba TM;Sunnen CN;Crowell B;Lee GH;Anderson AE;D'Arcangelo G
The phosphatase and tensin homologue on chromosome 10 (PTEN) suppresses the activity of the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, a signaling cascade critically involved in the regulation of cell proliferation and growth. Human patients carrying germline 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.
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影响因子:
25
作者:
Chow, David K.;Groszer, Matthias;Pribadi, Mochtar;Machniki, Michal;Carmichael, S. Thomas;Liu, Xin;Trachtenberg, Joshua T.
通讯作者:
Trachtenberg, Joshua T.
影响因子:
21.3
作者:
Potter, CJ;Pedraza, LG;Xu, T
通讯作者:
Xu, T
影响因子:
3.3
作者:
Fraser, M. M.;Bayazitov, I. T.;Baker, S. J.
通讯作者:
Baker, S. J.
影响因子:
4.3
作者:
Ljungberg, M. Cecilia;Sunnen, C. Nicole;D'Arcangelo, Gabriella
通讯作者:
D'Arcangelo, Gabriella
DOI:
10.1126/science.1199498
发表时间:
2011-06-10
期刊:
Science (New York, N.Y.)
影响因子:
--
作者:
Hsu PP;Kang SA;Rameseder J;Zhang Y;Ottina KA;Lim D;Peterson TR;Choi Y;Gray NS;Yaffe MB;Marto JA;Sabatini DM
通讯作者:
Sabatini DM