A mutation in mouse Disc1 that models a schizophrenia risk allele leads to specific alterations in neuronal architecture and cognition

被引：220

作者：

Kvajo, Mirna ^{[1
,3
]}

McKellar, Heather ^{[4
]}

Arguello, P. Alexander ^{[2
]}

Drew, Liam J. ^{[3
]}

Moore, Holly ^{[1
]}

MacDermott, Amy B. ^{[2
,3
]}

Karayiorgou, Maria ^{[1
]}

Gogos, Joseph A. ^{[2
,3
]}

机构：

[1] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY 10032 USA

[2] Columbia Univ, Med Ctr, Dept Neurosci, New York, NY 10032 USA

[3] Columbia Univ, Med Ctr, Dept Physiol & Cellular Biophys, New York, NY 10032 USA

[4] Columbia Univ, Integrated Program Cellular Mol & Biophys Studies, New York, NY 10032 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 19期

关键词：

bipolar disorder; gene; mouse model; working memory; adult neurogenesis;

D O I：

10.1073/pnas.0802615105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

DISC1 is a strong candidate susceptibility gene for schizophrenia, bipolar disorder, and depression. Using a mouse strain carrying an endogenous Disc1 orthologue engineered to model the putative effects of the disease-associated chromosomal translocation we demonstrate that impaired Disc1 function results in region-specific morphological alterations, including alterations in the organization of newly born and mature neurons of the dentate gyrus. Field recordings at CA3/CA1 synapses revealed a deficit in short-term plasticity. Using a battery of cognitive tests we found a selective impairment in working memory (WM), which may relate to deficits in WM and executive function observed in individuals with schizophrenia. Our results implicate malfunction of neural circuits within the hippocampus and medial prefrontal cortex and selective deficits in WM as contributing to the genetic risk conferred by this gene.

引用

页码：7076 / 7081

页数：6

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