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胆红素udp -葡萄糖醛酸糖基转移酶部分缺失而导致的非共轭高胆红素血症。分析了脐血中胆红素UDPglucuronosyltransferase基因的核苷酸序列。一些婴儿有由单核苷酸替换引起的错义突变，突变是杂合的。这些婴儿在该基因的启动子区域（estra TAin TATAA box）有异常。此外，还对Crigler-Najjar综合征I型和II型及Gilbert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，吉尔伯特综合症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。它们不仅存在于结缔组织中，也存在于中枢神经系统中，存在于细胞表面和细胞外空间。在发育中的大脑中，神经聚糖C、神经can、神经调节蛋白和两性素存在并受到精确的调节。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非蛋白聚糖形式，没有硫酸软骨素侧弯。在手术损伤的成年大鼠脑内，观察到胰岛素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回路形成等多种细胞过程中发挥重要作用。研究还表明，哺乳大鼠小脑神经元亚群具有不同种类的寡糖偶联两性素，并且在发育过程中偶联性发生显著变化。在外颗粒神经元细胞核内，寡糖偶联两性蛋白与凝集素样蛋白强结合，该复合物可能与DNA结合。无寡糖两性蛋白可溶于细胞核基质。

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.