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Detailed phenotype analyses of AD/HD model mutant mouse induced bv ENU.

机译:由ENU引起的AD / HD模型突变小鼠的详细表型分析。

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Attention deficits hyperactivity disorder (AD/HD) is a common behavioral disorder. The main symptoms of AD/HD are persistent inattention, hyperactivity, and impulsive behavior. These phenotypes often result in impaired social and academic performance. Preceding studies have provided strong evidence for a genetic component in the pathogenesis of AD/HD. However, while some evidence supports the involvement of suspect genes in AD/HD, contribution of each of genes remains ambiguous. Thus, various animal models for AD/HD are needed to be developed in order to elucidate pathogenesis of AD/HD. In RIKEN mouse ENU-mutagenesis project, we have been carrying out behavioral screening to develop novel models for AD/HD. In the project, M-174 mutant line was established as a candidate for genetic model of AD/HD. As a result of genetic analysis, we identified a misssense mutation in the Grinl gene that encodes NMDAR1. Further analysis revealed that M-174 mutant show hyperactivity in open-field and home-cage activity test, shorter duration of attention in object-exploration test, mild deficit in motor coordination in rotarod test. In addition, M-174 mutant mice displayed abnormal reaction to methylphenidate in open-field test and cFps expression in brain tissue. These results represent the validity of M-174 as a model for AD/HD.
机译:注意缺陷多动障碍(AD / HD)是一种常见的行为障碍。 AD / HD的主要症状是持续性注意力不集中,活动过度和冲动行为。这些表型通常会导致社会和学术表现受损。先前的研究为AD / HD发病机理中的遗传成分提供了有力的证据。然而,尽管一些证据支持可疑基因参与AD / HD,但每个基因的贡献仍然模棱两可。因此,需要开发用于AD / HD的各种动物模型,以阐明AD / HD的发病机理。在RIKEN小鼠ENU诱变项目中,我们一直在进行行为筛选以开发AD / HD的新型模型。在该项目中,建立了M-174突变体系作为AD / HD遗传模型的候选者。遗传分析的结果,我们在编码NMDAR1的Grinl基因中发现了一个错义突变。进一步的分析表明,M-174突变体在野外和笼笼活动测试中表现出过度活跃,在对象探索测试中表现出较短的注意力持续时间,在旋转脚架测试中表现出轻度的运动协调障碍。此外,M-174突变小鼠在野外试验中对哌醋甲酯表现出异常反应,并在脑组织中表达cFps。这些结果代表了M-174作为AD / HD模型的有效性。

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