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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 神经管闭合缺陷(NTDS)，特别是无脑儿和脊柱裂， 人类常见的先天缺陷。NTDS的风险在人类中是遗传的，但通常不是作为 单显性或隐性基因。NTDS的发病率因种族而异， 社会经济群体和时间，但仍然保持在1,000个出生率的数量级，尽管 妊娠早期补充叶酸的应用。因此，使用小鼠突变体和 与表型致病有关的菌株在我们对NTDS的理解中是非常关键的。 TFII-I是一种具有多个螺旋-环-螺旋重复结构域的转录因子。TFII-I 我们实验室培育的基因敲除小鼠表现出几种表型。 包括非专利药品。为了建立NTDS的分子基础，我们将寻找 下游靶基因受转录因子TFII-I家族调控。我们 相信这一类别中的某些基因可能会在 神经管关闭，因此很可能是NTDS的直接原因。 建立NTDS的发育遗传学基础的重要意义超出了 了解它会给神经管本身带来闭合。基因的鉴定 调节神经管发育允许进一步研究基因相互作用 可能与NTD条件有关。

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.