FUNCTION OF DLX GENES IN FOREBRAIN DEVELOPMENT

描述(摘自申请者摘要)：有充分的证据 建议精神分裂症和自闭症等神经精神障碍 在许多情况下是由影响发育的基因异常引起的 以及涉及认知和情绪的前脑神经系统的功能。 前脑最大的结构是大脑皮层和 纹状体；两者都被认为在神经精神疾病中起作用 精神错乱。我的研究目标是了解基因是如何调控的 纹状体和其他前脑结构的发育。为此，我的 实验室已经研究了DLX基因，它编码一个同源结构域家族 转录因子。有四个已知的DLX基因在 胚胎的前脑。本申请书的目的是续期一项于 我建议利用基因靶向技术研究DLX-1和DLX-2的功能 对小鼠的致突变作用(1 R01 MH51561-01A1)。我们已经完成了既定的目标。 发现同时缺乏DLX-1和-2的小鼠 有严重的基底节分化异常。该计划的目标是 本次资助申请中提出的实验主要集中在(1)充分 DIX-1、DLX-2和DLX-1、DLX-2突变体的表型特征 小鼠；(2)识别和表征在细胞周期中失控的基因 DLX-突变小鼠；(3)DLX、GSH和DLX基因互作的研究 Mash基因；以及(4)在DLX-5、DLX-6和DLX-5和-6上产生突变。

DESCRIPTION (Adapted from applicant's abstract): There is abundant evidence to suggest that neuropsychiatric disorders such as schizophrenia and autism are caused in many cases by genetic abnormalities that affect development and function of forebrain neural systems involved in cognition and emotion. The largest structures of the forebrain are the cerebral cortex and the striatum; both have been implicated as having a role in neuropsychiatric disorders. The goal of my research is to understand how genes regulate development of the striatum and other forebrain structures. To this end, my laboratory has studied the Dlx genes, which encode a family of homeodomain transcription factors. There are four known Dlx genes that are expressed in the embryonic forebrain. This application is for renewal of a grant in which I proposed to study the function of Dlx-1 and -2 using gene targeted mutagenesis in mice (1 R01 MH51561-01A1). We have accomplished the aims set out in that grant and have discovered that mice lacking both Dlx-1 and -2 have a severe abnormality of basal ganglia differentiation. The aims of the experiments proposed in this grant application are focused on (1) fully characterizing the phenotype of the Dix-1, Dlx-2 and Dlx-1 and -2 mutant mice; (2) identifying and characterizing genes that are dysregulated in the Dlx-mutant mice; (3) studying the genetic interactions of the Dlx, Gsh and Mash genes; and (4) making mutations in Dlx-5, Dlx-6 and Dlx-5 and -6.