Dominant-negative DISC1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans
Dominant-negative DISC1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans
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DOI：
10.1073/pnas.0704774104
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发表时间：
2007-09-04
影响因子：
11.1
通讯作者：
Sawa, Akira
中科院分区：
文献类型：
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作者：
Hikida, Takatoshi;Jaaro-Peled, Hanna;Sawa, Akira
在这里，我们报告的生成和表征分裂症-1（DISC 1）基因工程小鼠作为一个潜在的模型，主要精神疾病，如精神分裂症。DISC 1是一个有希望的主要精神疾病的遗传风险因素。在该转基因模型中，显性阴性形式的DISC 1（DN-DISC 1）在α CaMKII启动子下表达。DN-DISC 1小鼠的体内MRI检测到扩大的侧脑室，特别是在左侧，这表明与精神分裂症患者脑中发现的解剖结构的不对称变化有关。此外，在DN-DISC 1小鼠中观察到皮质中小清蛋白的免疫反应性的选择性降低，小清蛋白是可能导致皮质神经变性的中间神经元缺陷的标志物。这些结果表明，这些转基因小鼠可能被用作精神分裂症的模型。DN-DISC 1小鼠还表现出几种行为异常，包括多动、感觉运动门控和嗅觉相关行为障碍以及快感缺乏/抑郁样缺陷。
Here, we report generation and characterization of Disrupted-In-Schizophrenia-1 (DISC1) genetically engineered mice as a potential model for major mental illnesses, such as schizophrenia. DISC1 is a promising genetic risk factor for major mental illnesses. In this transgenic model, a dominant-negative form of DISC1 (DN-DISC1) is expressed under the alpha CaMKII promoter. in vivo MRI of the DN-DISC1 mice detected enlarged lateral ventricles particularly on the left side, suggesting a link to the asymmetrical change in anatomy found in brains of patients with schizophrenia. Furthermore, selective reduction in the immunoreactivity of parvalbumin in the cortex, a marker for an interneuron deficit that may underlie cortical asynchrony, is observed in the DN-DISC1 mice. These results suggest that these transgenic mice may be used as a model for schizophrenia. DN-DISC1 mice also display several behavioral abnormalities, including hyperactivity, disturbance in sensorimotor gating and olfactory-associated behavior, and an anhedonia/depression-like deficit.