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Project of Hereditary Keratinizing Disorders

遗传性角质化疾病项目

基本信息

批准号：
10557079
负责人：
YONEDA Kozo
金额：
$ 4.29万
依托单位：
AKITA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10557079/
关键词：
Transglutaminase Cell envelope loricrin セルエンベロープ遺伝性角化症葉状魚鱗癬

项目摘要

Transglutaminase 3 is an enzyme of which molecular weight is about 77 kDa. This enzyme is calcium-and thiol-dependent one and catalyze between lysine and glutamine residues of proteins. Therefore, iso-dipeptide crosslinks are made between cornified cell envelope protein precursors such as involucrin, small proline-rich proteins, elafin, cystatin A and loricrin. It is well known that transglutaminase 3 is distributed and granular layer of stratified epidermis. And this distribution pattern is almost same as loricrin.Keratinizing disorders in skin are divided in 2 major groups. One is hereditary keratinizing disorders and another is non-hereditary keratinizing ones. Hereditary keratinizing disorders are hereditary ichthyoses, Darier disease, palmoplantar hyperkeratosis, porokeratosis and so on. However, diseases such as bullous congenital ichthyosiform erythroderma, annular epidermolytic ichthyosis, lamellar ichthyosis, some of palmoplantar karatodermas, pachyonychia congenita, Vohwinkel syndrome, some of progressive systemic erythrokeratoderma, Darier disease and Hailey-Hailey disease are now known to be caused by deletions and/or point mutations of specific genes. In contrast, the responsible genes for most of the hereditary keratinizing disorders are not known. I postulate the gene for transglutaminase 3 enzyme is one of the responsible genes for the hereditary keratinizing disorders. I try to make the knock out mouse of transglutaminase 3 gene. We screened the mouse transglutaminase 3 cDNA from mouse epidermis cDNA library. We are going to get a clone of genomic DNA from 129SV mouse genomic library next and finally make a targeting vector.

转谷氨酰胺酶3是一种分子量约为77 kDa的酶。这种酶是钙和硫醇依赖性酶，在蛋白质的赖氨酸和谷氨酰胺残基之间进行催化。因此，异二肽交联是在角质化细胞包膜蛋白前体（例如外皮蛋白、富含脯氨酸的小蛋白、elafin、半胱氨酸蛋白酶抑制剂 A 和兜甲蛋白）之间形成的。众所周知，转谷氨酰胺酶3分布在复层表皮的颗粒层中。这种分布模式与兜甲素几乎相同。皮肤角质化疾病分为两大类。一种是遗传性角化病，另一种是非遗传性角化病。遗传性角化病有遗传性鱼鳞病、Darier病、掌跖角化过度症、汗孔角化症等。然而，诸如大疱性先天性鱼鳞病样红皮病、环状表皮松解性鱼鳞病、板层鱼鳞病、一些掌跖角皮病、先天性厚甲症、Vohwinkel综合征、一些进行性系统性红斑角皮病、Darier病和Hailey-Hailey病等疾病现在已知是由缺失引起的和/或特定基因的点突变。相比之下，大多数遗传性角质化疾病的相关基因尚不清楚。我推测转谷氨酰胺酶 3 酶的基因是遗传性角质化疾病的负责基因之一。我尝试制作转谷氨酰胺酶3基因敲除小鼠。我们从小鼠表皮cDNA文库中筛选了小鼠转谷氨酰胺酶3 cDNA。接下来我们将从129SV小鼠基因组文库中克隆基因组DNA，最后制作靶向载体。