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Innovation of novel treatments for various phenotypes of ichthyosis by restoration of ABCA12 lipid transporter gene expression

通过恢复ABCA12脂质转运蛋白基因表达来创新治疗各种表型鱼鳞病的新疗法

基本信息

批准号：
23249058
负责人：
AKIYAMA Masashi
金额：
$ 30.95万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2011
资助国家：
日本
起止时间：
2011-04-01 至 2014-03-31
项目状态：
已结题

项目摘要

In the present study, we established ABCA12-mutant mice harboring ABCA12 partial loss-of-function mutations, as model mice for congenital ichthyosiform erythroderma. In the model mice, we evaluated the up-regulation effects on ABCA12 gene expression by various compounds, which were expected to have up-regulation effects on ABCA12 gene expression. As for the compounds which were proved to have up-regulation effects on ABCA12 gene expression, we further investigated treatment efficacy of the up-regulators of ABCA12 gene expression in the model mice, by monitoring ichthyosis phenotype recovery and restoration of skin barrier function.In addition, we also established model mice carrying ABCA12 loss-of-function mutations as a model of harlequin ichthyosis. Using the model mice, we evaluated treatment efficacy of various read-through compounds to harlequin ichthyosis phenotypes by monitoring restoration of the stratum corneum barrier function and phenotype recovery.

在本研究中，我们建立了ABCA12突变小鼠携带ABCA12部分功能丧失突变，作为先天性鱼鳞病样红皮病的模型小鼠。在模型小鼠中，我们评估了各种化合物对ABCA 12基因表达的上调作用，这些化合物预期对ABCA 12基因表达具有上调作用。对于已证实对ABCA 12基因表达具有上调作用的化合物，我们通过监测鱼鳞病表型恢复和皮肤屏障功能恢复，进一步研究了ABCA 12基因表达上调剂在模型小鼠中的治疗效果。此外，我们还建立了携带ABCA 12功能缺失突变的模型小鼠作为丑角鱼鳞病模型。使用模型小鼠，我们通过监测角质层屏障功能的恢复和表型恢复来评估各种通读化合物对丑角鱼鳞病表型的治疗功效。

项目成果

期刊论文数量（42）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Severe chilblain lupus is associated with heterozygous missense mutations of catalytic amino acids or their adjacent in the exonuclease domains of 3' -repair exonuclease 1

严重冻疮性狼疮与 3-修复核酸外切酶 1 的核酸外切酶结构域中催化氨基酸或其相邻氨基酸的杂合错义突变有关

DOI：
发表时间：
2012
期刊：
J Invest Dermatol
影响因子：
6.5
作者：
Sugiura K;Takeichi T;Kono M;Ito Y;Ogawa Y;Muro Y;Akiyama M
通讯作者：
Akiyama M

LEDGF/DFS70 activates the MK2/IL6/STAT3 pathway in HaCaT

LEDGF/DFS70 激活 HaCaT 中的 MK2/IL6/STAT3 通路

DOI：
10.1016/j.jdermsci.2011.05.004
发表时间：
2011
期刊：
J Dermatol Sci
影响因子：
4.6
作者：
Tazawa H;Irei T;Igarashi Y;Tanaka Y;Ohdan H;Suda T;Takeichi T
通讯作者：
Takeichi T

Type VII collagen deficiency causesdefective tooth enamel formation due to poor differentiation of ameloblasts

由于成釉细胞分化不良，VII 型胶原蛋白缺乏会导致牙釉质形成缺陷

DOI：
10.1016/j.ajpath.2012.07.018
发表时间：
2012
期刊：
Am J Pathol
影响因子：
6
作者：
Umemoto H;Akiyama M;Domon T;Nomura T;Shinkuma S;Ito K;Asaka T;Sawamura D;Uitto J;Uo M;Kitagawa Y;Shimizu H
通讯作者：
Shimizu H

A novel ATP2C1 early truncation mutation suggests haploinsufficiency as a pathogenic mechanism in a patient with Hailey-Hailey disease.