Preparation and application of mouse model for the study on chaperone therapy for Fabry disease

本研究的目的是建立Fabry病分子伴侣治疗的小鼠模型。法布里病是一种遗传性疾病，由α-半乳糖苷酶A活性缺陷引起，并导致鞘糖脂，主要是神经酰胺三己糖苷（Gb 3）的积累。先前建立的小鼠模型对于酶活性的测定是良好的，但对于Gb 3对候选药物的作用的积累不是很好。在本研究中，我们制备了表达人Gb 3合酶基因的转基因小鼠，并且我们成功地建立了小鼠模型，其中我们可以确定化合物对酶活性和Gb 3含量的影响。

The purpose of our study is to establish a mouse model for the chaperone therapy for Fabry disease. Fabry disease is an inherited disease caused by the deficient activity of α-galactosidase A and resulted to accumulation of glycosphingolipid, predominantly globotriaosylceramide (Gb3). The mouse model established previously was good for the determination of enzyme activity but not for the accumulation of Gb3 on the effect of drug candidates. In our present study, we prepared the transgenic mouse expressing human Gb3 synthase gene, and we succeeded a mouse model in which we can determine the effect of compounds on both enzyme activity and Gb3 content.