Abstract
Abstract: :
ARVO 2002 Abstract Purpose: The human X–linked cataract dental (XLCD) syndrome (also called Nance Horan) is an X–linked disorder characterized by congenital cataract, microcornea and dental anomalies. XLCD has been mapped to the region of Xp22.2, between markers DXS85 and DXS1226. The mutant Xcat mouse also displays congenital cataracts (evident by prenatal day 14) and the mutation in Xcxat maps to a region of the mouse X chromosome that is syntenic with human Xp22. For these reason's Xcat is the best animal model for human XLCD. We previously mapped the genetic position of Xcat through an interspecific backcross and identified two markers DxWas31 and DxPas18 that show no recombination with Xcat. We have used these markers to screen a mouse bacterial artificial chromosome (BAC) library from CJ7/129SV mice. This BAC library screen has resulted in the development of a 900kb BAC contig map of the Xcat critical region, composed of 6 overlapping BAC's, ranging in size from 80Kb to 250Kb. Through the NIH Mouse Sequencng Inititative, we obtained draft–quality sequence of each of the six BAC's within the Xcat contig. We performed gene prediction analysis, as well as BLAST searches against EST databases and identified at least 7 transcription units within the Xcat BAC contig, one of which could potentially contain the Xcat gene. We are screening these genes for expression in the lens, conservation across species and expression in mutant Xcat mice. In addition, we are performing BAC complementation experiments to look for BAC's that rescue Xcat mutant mice from the cataract phenotype. Identifying the Xcat gene will contribute to the our understanding of the molecular events involved in lens development and cataractogenesis
Keywords: cataract • genetics