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

在本研究中，我们建立了携带ABCA12部分功能缺失突变的ABCA12突变小鼠，作为先天性鱼鳞状红皮病的模型小鼠。在模型小鼠中，我们评估了不同化合物对ABCA12基因表达的上调作用，这些化合物有望对ABCA12基因表达产生上调作用。对于已证实对ABCA12基因表达有上调作用的化合物，我们通过监测鱼鳞病的表型恢复和皮肤屏障功能的恢复，进一步研究了ABCA12基因表达上调在模型小鼠中的治疗效果。此外，我们还建立了携带ABCA12功能缺失突变的小鼠作为小丑鱼鳞病的模型。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不同的通读化合物对小丑鱼鳞病表型的治疗效果。

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.