Genetic Manipulation of Lens Connexin Diversity

Abstract

Abstract: : Purpose: Determine the contributions of the gap junction proteins Cx46 and Cx50 to lens growth and homeostasis. Methods: Mice were engineered with a targeted deletion of Cx50, or a targeted replacement of Cx50 with Cx46 (Cx50KI46). Growth rates were measured by BrdU incorporation. Lenses were analyzed by microscopic and biochemical means. Results: Deletion of Cx50 resulted in microphthalmia and cataract. Targeted substitution of Cx46 for Cx50 produced lenses lacking connexin diversity, but without a reduction in channel quantity. Lenses of Cx50 deficient mice failed to grow normally even when Cx46 was provided as a functional substitute. However, Cx46 substitution did prevent cataract formation that occurred after simple deletion of Cx50. Conclusion: Cx50 is absolutely required for proper lens growth, but Cx46 can replace Cx50 to maintain lens clarity and homeostasis.  

Keywords: 340 cell-cell communication • 316 animal model • 338 cataract