Early Cataract Formation in Bin3 Knockout Mice

Abstract

Abstract: : Purpose: Congenital cataracts are responsible for nealy 10% of all visual loss in children worldwide. It is estimated that 1 in 250 newborns has some form of cataract. The cause of the vast majority of cataracts is unknown. BAR (Bin/Amphiphysin/RVS) adapter proteins have been suggested to regulate endocytosis, actin polymerization, apoptosis, and transcription, but their precise biological roles remain obscure. At least five mammalian genes that encode BAR adapter proteins, including the evolutionarily conserved and ubiquitously expressed Bin1/Amphyphysin–II, and Bin3 genes. To further characterize the function and possible role of Bin3 in tumorogenesis, knockout mice were created. Methods: Knockout mice were created according to standard procedures. The histopathology of Bin3–null and wild type mouse eyes are compared en bloc with particular attention to the lens. Results: Unexpectedly, we discovered that the knockout mice develop early cataracts. This highly penetrant phenotype has been observed in all 25 of the Bin3–null mice examined to date. No other pathology has been identified in these mice. We examined the lenses of these mice and found vacuolar degeneration and calcification along the lens fibers. Conclusions: This is the first reported demonstration of Bin3 gene loss causing cataract formation. Future investigation will focus on better understanding the function of Bin3 in eye development and its role, if any, in the pathogenesis of human cataracts.

Keywords: cataract • genetics • pathology: experimental