Characterization of ddY cataract mouse as a new animal model

本研究旨在阐明ddY小鼠遗传性白内障的特征。为了阐明遗传模式，对ddY白内障和正常ddY小鼠之间的F1和F2杂种进行了分析。白内障在突变体的6 ~ 8周龄发生，而在杂种F1中没有发生。在F2杂种中，患病小鼠与未患病小鼠的比例为1：3。白内障的发病率无性别差异。因此，白内障是由常染色体隐性基因遗传的。免疫组化法检测成纤维细胞生长因子（FGF）和转化生长因子β（TGF-β）的表达，SDS-PAGE法检测透镜蛋白的表达。FGF和TGF-β在生后3 ~ 6周表达增强。在白内障小鼠中表达降低的蛋白质之一是β-晶状体蛋白B1。这些结果表明，该特征被认为是通过常染色体隐性模式遗传的，并且在该模型中，β-晶状体蛋白B1的减少以及FGF和TGF-β表达的增加在很大程度上参与了白内障的诱导。通过连锁分析，将白内障基因定位于D2 mit 467、515（DNA微卫星标记）与线粒体核糖体再循环因子（基因）之间1.21cM的区域。提示ddY白内障小鼠是一种新的白内障模型小鼠，为白内障的遗传分析和分子生物学研究提供了良好的工具。

The present study was designed to clarify the characters of inherited cataract of the ddY mice. For elucidation of the mode of inheritance, F1 and F2 hybrids between ddY cataract and normal ddY mice were analyzed. The cataract developed from 6 to 8 weeks old in the mutant but did not in the F1 hybrids. The ratio of affected to unaffected mice was 1:3 in the F2 hybrid. There was no sex difference in the incidence of the cataract. Therefore, the cataract is inherited by an autosomal recessive gene. The expressions of FGF and TGF-β were investigated by immunohistochemistry and the expression of lens protein by SDS-PAGE. The expressions of FGF and TGF-β were increased 3 to 6 weeks after birth. One of proteins that have decreased expression in cataract mice was β-crystallin B1. These findings revealed that the character is considered to be inherited by the autosomal recessive mode and that both the decrease in β-crystallin B1 and increase in FGF and TGF-β expressions are largely involved in the induction of cataract in this model. By linkage analysis, the cataract gene was localized in the region of 1.21 cM between D2mit 467, 515 (DNA microsatellite markers) and mitochondrial ribosome recycling factor (gene). These findings revealed that the ddY cataract mouse is new cataract model mouse and will be a good tool for genetic analysis and study of molecular biology of cataractogenesis.