Project Summary Genetic variances, environmental stress factors and aging can initiate pathological conditions in lens cells leading to different types of cataracts. Previous studies show that the postnatal onset and severity of lens nuclear cataracts are impacted by a functional loss of connexin 46 (Cx46) with genetic variances including CP49 and periaxin (Prx) occurred between mouse strains C57BL/6J (B6) and 129 Svjae (129). This research proposal will evaluate novel hypotheses about how intercellular gap junctions consisting of Cx46 and Prx mediated membrane/cytoskeletal complexes coordinately regulate interior lens fiber cell morphogenesis and calcium homeostasis needed for lens transparency. This project will provide a comprehensive mechanistic understanding about how calcium influx and efflux as well as interlocking structures of lens fibers are regulated and maintained by the adhesion and transport mosaic systems including gap junctions, Aqp0, calcium channels linked to cytoskeletons through scaffold proteins such as Prx. Completion of this research project will also provide essential knowledge about genetic variations among common mouse strains such as C57BL/6J and 129 to the lens research community.