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

吉尔伯特综合征的特征是由于部分缺乏胆红素UDP-葡萄糖醛酸转移酶引起的非结合型高胆红素血症。在脐带血中分析胆红素UDP葡萄糖醛酸基转移酶基因的核苷酸序列。部分婴儿存在由单个核素取代引起的错义突变，且突变为杂合突变。这些婴儿在基因的启动子区域有异常（TATAA盒中的estra TA）。此外，分析了Crigler-Najjar综合征I型和II型患者以及吉尔伯特综合征患者的亲属。所有轻度高胆红素血症的亲属都是每个缺陷等位基因的杂合子。这些结果表明，吉尔伯特综合征是一种显性遗传特征。蛋白多糖是细胞外基质和细胞膜的一些主要成分。它们不仅存在于结缔组织中，也存在于中枢神经系统中，位于细胞表面和细胞外。在发育中的脑中，神经聚糖C、神经聚糖、神经调节蛋白和神经节苷脂蛋白是存在的并且被精确地调节。随着小脑发育的进行，神经聚糖C的结构从蛋白聚糖形式变为非蛋白聚糖形式，而没有硫酸软骨炎侧链。在手术损伤的成年大鼠脑中观察到硫酸软骨素结合的神经调节蛋白的快速出现。多糖侧链在细胞增殖和神经回路形成等细胞过程中发挥重要作用。乳鼠小脑神经元各亚群均具有不同类型的寡糖结合型磷脂，且其结合方式在发育过程中发生显著变化。在外颗粒神经元核内，寡糖结合的凝集素与凝集素样蛋白质强烈结合，形成的复合物可能与DNA结合。无寡糖的白藜芦醇苷可溶于细胞核基质中。

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.