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Neuronal migration : its mechanism in normal development and pathologic changes in cerebral dysgenesis.

神经元迁移：其正常发育和脑发育不全病理变化的机制。

基本信息

批准号：
10670753
负责人：
MIZUGUCHI Masashi
金额：
$ 2.05万
依托单位：
Jichi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670753/
关键词：
Lissencephaly Subcortical laminar heterotopia Fukuyama type congenital muscular dystrophy Tuberous sclerosis doublecortin DCAMKL1 hamartin fukutin LIS1 Ekerラット Zellweger症候群 tuberin telencephalin 全前脳症

项目摘要

1) Doublecortin is a product of the DCX gene responsible for X-linked lissencephaly and subcortical laminar heterotopia syndrome. DCAMKL 1 (or KIAA0369) is a calcium calmodulin-dependent kinase with high homology to doublecortin. We produced specific antibodies against these proteins, and studied their expression immunochemically and immunohistochemically. The results indicated specific expression of these proteins in the normally developing nervous system during the fetal period. Intense immunoreactivity was localilzed in migrating neurons. In migration disorders, doublecortin expression was downregulated in brains with Zellweger syndrome and in subcortical laminar heterotopia, whereas in those with tuberous sclerosis some abnormal giant cells showed its overdue expression.2) Fukuyama type congenital muscular dystrophy (FCMD) is caused by a mutaion in the fukutin gene. We produced antibodies against fukutin protein, and studied its expression immunochemically and immunohisto-chemically. In brains of normal fetuses, high expression was noted in the granular layer at the cerebral surface, whereas fukutin was decreased in those of FCMD fetuses.3) Tuberous sclerosis (TS) is caused by a mutation in either of the two tumor suppressor genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively. In this study, we produced antibodies against hamartin, and studied its expression immunochemically and immunohisto- chemically. In the brain, kidney and heart of control patients, hamartin and tuberin co-localized. They showed simlutaneous loss in TS brain lesions, as well as in TS-associated renal and cardiac hamartomas. The brains of Eker rats, an animal model of TSC2, were studied pathologically. Two novel brain lesions, cortical tuber and anaplastic ganglioglioma, were found.

1)Doublecortin是DCX基因的产物，负责X连锁无脑畸形和皮质下层状异位综合征。DCAMKL 1（或KIAA0369）是一种钙钙调蛋白依赖性激酶，与doublecortin具有高度同源性。我们生产了针对这些蛋白质的特异性抗体，并研究了它们的表达免疫化学和荧光化学。结果表明，这些蛋白质在胎儿时期正常发育的神经系统中特异性表达。强烈的免疫反应定位于迁移神经元。在移行障碍中，双皮质素在Zellweger综合征和皮质下层状异位中表达下调，而在结节性硬化症中，一些异常的巨细胞显示其逾期表达。2）Fukuyama型先天性肌营养不良（FCMD）是由Fukuyama基因突变引起的。我们制备了抗fukarin蛋白的抗体，并研究了其表达的免疫化学和荧光化学。在正常胎儿的大脑中，在大脑表面的颗粒层中观察到高表达，而在FCMD胎儿中，fukarin减少。3）脑硬化症（TS）是由两种肿瘤抑制基因中的任一种突变引起的，TSC 1和TSC 2，分别编码hamartin和tuberin。在这项研究中，我们产生了针对hamartin的抗体，并研究了其表达的免疫化学和免疫组织化学。在对照组患者的脑、肾和心脏中，hamartin和tuberin共定位。他们显示TS脑病变以及TS相关的肾和心脏错构瘤同时丢失。对TSC 2的动物模型Eker大鼠的脑进行病理学研究。两个新的大脑病变，皮质结节和间变性神经节胶质瘤，被发现。