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连锁的Lissencephaly和皮层层状层状杂质综合征。 DCAMKL 1（或KIAA0369）是钙钙调蛋白依赖性激酶，具有高doublecortin的同源性。我们对这些蛋白质产生了特定的抗体，并通过免疫化学和免疫组织化学研究了它们的表达。结果表明，在胎儿时期，这些蛋白质在正常发展的神经系统中的特异性表达。强烈的免疫反应性被迁移到神经元中。在迁移障碍中，Zellweger综合征和皮质下层状杂质杂质症中的双核素表达被下调，而在患有结节性硬化症的患者中，某些异常巨细胞表现出了过度的表达。我们产生了针对富丁蛋白蛋白的抗体，并通过免疫化学和免疫史学研究了其表达。在正常胎儿的大脑中，在脑表面的颗粒状层中发现了高表达，而FCMD胎儿的富丁蛋白则降低。3）结节性硬化症（TS）是由两种肿瘤抑制基因，TSC1和TSC2中的任何一个中的任何一种突变引起的，这些突变是由TSC1和TSC2中的两种，它们的结构化hamartin和Tuberin和Tuberin和Tuberin cyberin和Tuberin均相应。在这项研究中，我们产生了针对Hamartin的抗体，并以化学的方式研究了其表达。在大脑，对照患者的肾脏和心脏中心，Hamartin和Tuberin共定位。他们显示出TS脑损伤以及与TS相关的肾脏和心脏障碍的同样丧失。 Eker大鼠的大脑是TSC2的动物模型，从病理上进行了研究。发现了两种新型的脑病变，即皮质块茎和变形神经节瘤。