权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Analysis of genes for UDP-GT in Gilbert's sundrome and of neonatal cerebellar disorganization in model animals

吉尔伯特综合症和模型动物新生儿小脑紊乱的 UDP-GT 基因分析

基本信息

批准号：
11670811
负责人：
KEINO Hiroomi
金额：
$ 2.3万
依托单位：
Institute for Developmental Research, Aichi Human Service Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

Gilbert's syndrome is characterised by unconjugated hyperbilirubinemia due to partial absence of bilirubin UDP-glucuronosyltransferase. Nucleotide sequences of the genes for bilirubin UDPglucuronosyltransferase were analysed in umbilical blood. Some babies had a missense mutations coused by a single nucliotide substitution and the mutations were heterozygous. The babies had an abnormality in the promoter region of the gene (estra TAin TATAA box). In addition, relatives of patients with Crigler-Najjar syndrome Type I and II, and those with Gilbert's syndrome were analysed. All relatives with mild hyperbilirubinemia were heterozygotes with respect to each defective allele. These results suggest that Gilbert's syndrome is inherited as a dominant trait.Proteoglycans are some of the major constituents of the extra cellular matrix and cell membranes. They are located at cell surface and extra cellular space, not only in connective tissues but also in central nervous system. In developing brain, neuroglycan C, neurocan, neuregulin, and amphoterin are presnt and preisely regulated. The structure of neuroglycan C changes from a proteoglycan form to a nonproteoglycan form without chondroiti sulfate side chanis as the cerebellar development proceeds. The rapid appearance of chondroitinsulfate conjugated neuregulin was observed in the adult rat brain which was surgically injured. The poly saccharide side chain may play important roles in various cellular processes such as cell proliferation and neuronal circuits formation. It is also showed that the subsets of suckling rat cerebellar neurons possess different classes of oligosaccharide conjugated amphoterin, and their conjugation dramatically changes during the developmental prograss. In the nucleus of external granule neuron, oligosaccharide conjugated amphoterin strongly combined with lectin-like proteins, then the complex may combined with DNA. The oligosaccaride-free amphoterin are soluble in the matrix of nucleus.

吉尔伯特综合征的特征是由于胆红素UDP-葡萄糖醛酸基转移酶部分缺失而导致的非结合高胆红素血症。对脐血中胆红素UDP葡萄糖醛酸基转移酶基因的核苷酸序列进行了分析。一些婴儿存在由单个核苷酸取代引起的错义突变，并且突变是杂合的。这些婴儿的基因启动子区域（TATAA 盒中的 estra TA）存在异常。此外，还对 I 型和 II 型克里格勒-纳贾尔综合征患者以及吉尔伯特综合征患者的亲属进行了分析。所有患有轻度高胆红素血症的亲属对于每个缺陷等位基因都是杂合子。这些结果表明吉尔伯特综合征是作为显性特征遗传的。蛋白聚糖是细胞外基质和细胞膜的一些主要成分。它们位于细胞表面和细胞外空间，不仅存在于结缔组织中，而且存在于中枢神经系统中。在发育中的大脑中，神经聚糖 C、神经聚糖、神经调节蛋白和两性蛋白存在并受到预先调节。随着小脑发育的进行，神经聚糖C的结构从蛋白聚糖形式转变为没有硫酸软骨素侧链的非蛋白聚糖形式。在手术损伤的成年大鼠脑中观察到硫酸软骨素结合神经调节蛋白的快速出现。多糖侧链可能在细胞增殖和神经元回路形成等各种细胞过程中发挥重要作用。研究还表明，乳鼠小脑神经元亚群具有不同类别的寡糖缀合两性蛋白，并且它们的缀合在发育过程中发生显着变化。在外颗粒神经元的细胞核中，寡糖缀合的两性蛋白与凝集素样蛋白强烈结合，然后该复合物可能与DNA结合。不含寡糖的两性蛋白可溶于细胞核基质。