TARGETED DISRUPTION OF EMXL GENE ACTIVITY

本提案中描述的实验旨在检查 小鼠Emx1基因在大脑发育中的作用emx1表示 在胚胎发育早期前脑的有限区域。 Emx1包含一个同源异型盒，使其基因产物能够结合 DNA和潜在的调节转录。图案形成在 脊椎动物中枢神经系统依赖于区域表达， 调节转录的基因的活性;这些实验将 测试Emx1是否可能是在图案形成中活跃的基因。EMX1 将使用基因靶向来破坏活性， 基因在体内。 然后分析动物的解剖学和 基因突变导致的行为改变 如果Emx 1起作用， 在模式形成过程中，很可能会指定区域身份 它在大脑中表达的部分;解剖学上的重排 这个区域的大小将决定前脑是否需要Emx 1活动 为了它的发展。一个密切相关的人类基因EMX2的突变 基因，与中脑畸形有关，这表明需要 EMX2蛋白在中枢神经系统中的适当细胞迁移 发展 Emx1基因可能也是 前脑发育：拟议的实验将测试这一点。 假设和定义如何和Emx1在发展过程中的作用。 在突变小鼠中鉴定的缺陷与临床的缺陷的比较 关于人类大脑缺陷的信息可能会揭示先天性 与人类EMX1基因突变有关的脑部疾病。

The experiments described in this proposal are designed to examine the role of the mouse Emx1 gene during brain development. Emx1 is expressed in a limited region of the forebrain during early embryonic development. Emx1 contains a homeobox, giving its gene product the ability to bind DNA and potentially to regulate transcription. Pattern formation in the vertebrate central nervous system relies on the regional expression and activity of genes which regulate transcription; these experiments will test whether Emx1 may be a gene active in pattern formation. Emx1 function will be studied using gene targeting to disrupt the activity of the gene in vivo. Animals will then be analyzed for anatomical and behavioral changes stemming from engineered mutation. If Emx1 acts during pattern formation, it is likely to specify the regional identity of part of the brain in which it is expresses; anatomical rearrangements of this area will define whether the forebrain requires Emx1 activity for its development. Mutations in a closely related human gene, the EMX2 gene, are linked to schizencephaly, suggesting a requirement for the EMX2 protein for proper cell migration during central nervous system development. It is likely that the Emx1 gene is also critical for anterior brain development: the proposed experiments will test this hypothesis and define how and where Emx1 acts during development. Comparison of the defects identified in mutant mice with clinical information about brain defects in humans may then uncover congenital brain disorders which are linked to mutations in the human EMX1 gene.