THE ROLE OF TFII-I TRANSCRIPTION FACTOR IN THE NEURAL TUBE CLOSURE DEFECTS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。神经管闭合缺陷（NTDs），特别是无脑儿和脊柱裂，是常见的人类出生缺陷。被忽视热带病的风险在人类中是遗传的，但通常不是单一的显性或隐性基因。被忽视热带病的发病率因种族、社会经济群体和时间而异，但尽管在妊娠早期使用叶酸补充剂，但仍保持在千分之一的水平。因此，使用与表型因果关系相关的小鼠突变体和菌株对于我们理解ntd非常关键。TFII-I是一种具有多个螺旋-环-螺旋重复结构域的转录因子。我们实验室产生的TFII-I基因敲除小鼠表现出包括NTDs在内的几种表型表现。为了建立ntd的分子基础，我们将寻找TFII-I转录因子家族调控的下游靶基因。我们认为，这一类的某些基因可能在神经管闭合中被严重地解除了调控，因此最有可能是ntd的直接原因。ntd的发育遗传学基础的建立比神经管闭合本身的理解更重要。调控神经管发育的基因的鉴定允许进一步研究可能导致NTD病情的遗传相互作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Neural tube closure defects (NTDs), in particular anencephaly and spina bifida, are common human birth defects. Risk of NTDs is inherited in humans, but usually not as a single dominant or recessive gene. The incidence of NTDs varies with ethnic group, socioeconomic group and time, but remains on the order of 1 in 1,000 births, despite the use of folate supplementation in early pregnancy. Thus, the use of mouse mutants and strains implicated in phenotype causation is very critical in our understanding of NTDs. TFII-I is a transcription factor with multiple helix-loop-helix repeat domains. The TFII-I knockout mice generated in our laboratory display several phenotypic manifestations including NTDs. In an effort to establish the molecular basis of NTDs, we will search for the downstream target genes regulated by the TFII-I family of transcription factors. We believe that certain set of genes in this category may be profoundly deregulated in the neural tube closure and are therefore most probably the immediate causal factors in NTDs. The establishment of the developmental genetic basis of NTDs is important beyond the understanding it brings to neural tube closure itself. The identification of genes that regulate neural tube development allows further investigation of genetic interactions that may be causal to NTD conditions.