Expression of the G72/G30 gene in transgenic mice induces behavioral changes.
Expression of the G72/G30 gene in transgenic mice induces behavioral changes.
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G72/G30基因在转基因小鼠中的表达诱导行为变化。
DOI：
10.1038/mp.2012.185
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发表时间：
2014-02
影响因子：
11
通讯作者：
Liu, C.
中科院分区：
文献类型：
--
作者：
Cheng, L.;Hattori, E.;Nakajima, A.;Woehrle, N. S.;Opal, M. D.;Zhang, C.;Grennan, K.;Dulawa, S. C.;Tang, Y-P;Gershon, E. S.;Liu, C.
关键词：
G72/G30基因复合体是精神分裂症和双相情感障碍的候选基因。然而，G72 和 G30 mRNA 在人脑中的表达水平非常低，仅观察到罕见的剪接形式。我们在此报告 G72/G30 转基因小鼠模型中的 G72/G30 表达谱和行为变化。使用含有G72/G30基因组区域的人BAC克隆建立转基因小鼠模型，并对其进行基因表达研究、蛋白质印迹和行为测试。相对于它们在人类中的最低表达，G72和G30 mRNA在转基因小鼠中高表达，并且具有更复杂的剪接模式。 G72 转录水平最高的是睾丸，其次是大脑皮层，其他组织中的水平非常低或检测不到。在转基因小鼠中未检测到 LG72（G72 的长推定亚型）蛋白。全基因组表达谱鉴定出 361 个基因在转基因小鼠中与野生型小鼠差异表达，其中包括先前与神经和心理疾病有关的基因。与野生型小鼠相比，转基因小鼠在旷场测试中表现出较少的刻板运动，在前脉冲抑制测试过程中表现出较高的基线惊吓反应，在蔗糖偏好测试中表现出较低的享乐反应。转录组谱的变化和多种小鼠行为效应表明，G72 基因可能在调节与精神疾病相关的行为中发挥作用。
The G72/G30 gene complex is a candidate gene for schizophrenia and bipolar disorder. However, G72 and G30 mRNAs are expressed at very low levels in human brain, with only rare splicing forms observed. We report here G72/G30 expression profiles and behavioral changes in a G72/G30 transgenic mouse model. A human BAC clone containing the G72/G30 genomic region was used to establish the transgenic mouse model, on which gene expression studies, Western blot and behavioral tests were performed. Relative to their minimal expression in humans, G72 and G30 mRNAs were highly expressed in the transgenic mice, and had a more complex splicing pattern. The highest G72 transcript levels were found in testis, followed by cerebral cortex, with very low or undetectable levels in other tissues. No LG72 (the long putative isoform of G72) protein was detected in the transgenic mice. Whole-genome expression profiling identified 361 genes differentially-expressed in transgenic mice compared to wild-type, including genes previously implicated in neurological and psychological disorders. Relative to wild-type mice, the transgenic mice exhibited fewer stereotypic movements in the open field test, higher baseline startle responses in the course of the prepulse inhibition test, and lower hedonic responses in the sucrose preference test. The transcriptome profile changes and multiple mouse behavioral effects suggest that the G72 gene may play a role in modulating behaviors relevant to psychiatric disorders.
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影响因子：
4.4
作者：
Benzel, Isabel;Kew, James N. C.;Maycox, Peter R.
通讯作者：
Maycox, Peter R.
DOI：
10.1002/ajmg.b.30181
发表时间：
2005-07-05
影响因子：
2.8
作者：
Hong, LE;Wonodi, I;Thaker, GK
通讯作者：
Thaker, GK
DOI：
10.1176/appi.ajp.2010.10040484
发表时间：
2010-12
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Feyder M;Karlsson RM;Mathur P;Lyman M;Bock R;Momenan R;Munasinghe J;Scattoni ML;Ihne J;Camp M;Graybeal C;Strathdee D;Begg A;Alvarez VA;Kirsch P;Rietschel M;Cichon S;Walter H;Meyer-Lindenberg A;Grant SG;Holmes A
通讯作者：
Holmes A
影响因子：
6.6
作者：
Craddock, N;O'Donovan, MC;Owen, MJ
通讯作者：
Owen, MJ
影响因子：
2.8
作者：
Borsotto, M.;Cavarec, L.;Chumakov, I.
通讯作者：
Chumakov, I.