FUNCTION OF DLX GENES IN FOREBRAIN DEVELOPMENT

描述（改编自申请人摘要）：有充分的证据 表明精神分裂症和自闭症等神经精神疾病 在许多情况下是由影响发育的遗传异常引起的 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病学中起作用 紊乱 我研究的目标是了解基因是如何调节 纹状体和其他前脑结构的发育。 为此，我 一个实验室研究了Dlx基因，它编码一个同源结构域家族， 转录因子 有四种已知的Dlx基因在大肠杆菌中表达， 胚胎前脑 本申请书是为一项在 我建议用基因靶向技术研究Dlx-1和Dlx-2的功能， 在小鼠中的诱变（1 R 01 MH 51561 - 01 A1）。 我们已经达到了既定的目标 并发现缺乏Dlx-1和Dlx-2的小鼠 基底神经节分化严重异常 的目标 在这个补助金申请中提出的实验集中在（1）完全 表征Dix-1、Dlx-2和Dlx-1和Dlx-2突变体的表型 小鼠;（2）鉴定和表征在小鼠中失调的基因， Dlx突变小鼠;（3）研究Dlx、Gsh和 Mash基因;和（4）在Dlx-5、Dlx-6和Dlx-5和Dlx-6中进行突变。

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.