Research for the causative genes of the congenital abnormality using analysis of the action points of teratogenic factors

据认为，半数以上的先天性缺陷是遗传因素和环境因素共同作用的结果。本文分析了研究环境因素作用机理的新方法。近两年，我们用基因陷阱法在培养细胞中筛选过表达基因的靶基因，并分析其在体内的表达模式；2)筛选脊椎动物畸形等遗传性疾病的致病基因。1)利用ES细胞和软骨细胞祖细胞ATDC5细胞系筛选Pax1/9的靶基因。我们检测到两个基因，Pumilio和Siena作为候选靶基因。分析这些基因在正常和突变小鼠胚胎中的表达模式，以检测转录调控。2)分析2例诊断为Jarcho-Levin综合征的患者的致病基因Dll-3，该基因正在进行中。对疑似Schwarz-Jampel综合征患者的Pumilio基因进行了分析，发现该基因定位于该病的关键区域，但证实该病是由2000年Perlecan基因突变引起的。

It is believed that more than half of the congenital defects is caused with the interaction between genetic factors and circumstance factors. In this report, we analyzed the new method how to approach the action mechanism of the circumstance factors.In last two years, 1) we screened the target genes of the overexpressed gene in the cultured cells with gene trap method and analyzed their in vivo expression pattern, 2) we screened the causative genes of the inherited diseases including vertebrate deformity.1) We used ES cells and ATDC5 cell line, progenitor of chondrocyte, for the screening of target genes of Pax1/9. We detected two genes, Pumilio and Siena, as candidate target gene. These genes are analyzed expression pattern in both of normal and mutant mouse embryos, in order to detect the regulation of transcription.2) Two patients diagnosed as Jarcho-Levin syndrome are analyzed in its causative gene, Dll-3, which is in progress. The patient suspected as Schwarz-Jampel syndrome is analyzed in Pumilio gene, which is found to be mapped to critical region of this disease, however, it is proved that this disease is caused with the mutation of Perlecan in 2000.