Specific developmental disruption of disrupted-in-schizophrenia-1 function results in schizophrenia-related phenotypes in mice
Specific developmental disruption of disrupted-in-schizophrenia-1 function results in schizophrenia-related phenotypes in mice
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DOI：
10.1073/pnas.0706900104
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发表时间：
2007-11-13
影响因子：
11.1
通讯作者：
Cannon, Tyrone D.
中科院分区：
文献类型：
--
作者：
Li, Weidong;Zhou, Yu;Cannon, Tyrone D.
DISC 1最初是通过平衡易位（1;11）（q42.1;q14.3）发现的，该易位导致DISC 1蛋白C末端的丢失，该区域被认为在大脑发育中起重要作用。在这里，我们使用一种诱导型和可逆的转基因系统，以证明早期出生后，但不是成年诱导，在小鼠中的DISC 1的C-末端部分的结果在一组精神分裂症相关的表型，包括海马树突的复杂性降低，抑郁样性状，异常的空间工作记忆，并减少社交。因此，我们报告说，与精神分裂症以及工作记忆障碍和灰质密度降低相关的DISC 1单倍型的不一致双胞胎样本中的个体比那些没有单倍型的个体更容易表现出社交能力的缺陷。我们的研究结果表明，在大脑发育过程中DISC 1功能的改变有助于精神分裂症的发病机制。
Disrupted-in-schizophrenia 1 (DISC1) was initially discovered through a balanced translocation (1;11)(q42.1;q14.3) that results in loss of the C terminus of the DISC1 protein, a region that is thought to play an important role in brain development. Here, we use an inducible and reversible transgenic system to demonstrate that early postnatal, but not adult induction, of a C-terminal portion of DISC1 in mice results in a cluster of schizophrenia-related phenotypes, including reduced hippocampal dendritic complexity, depressive-like traits, abnormal spatial working memory, and reduced sociability. Accordingly, we report that individuals in a discordant twin sample with a DISC1 haplotype, associating with schizophrenia as well as working memory impairments and reduced gray matter density, were more likely to show deficits in sociability than those without the haplotype. Our findings demonstrate that alterations in DISC1 function during brain development contribute to schizophrenia pathogenesis.