Maintenance of transparency of the avascular lens depends on regulated ionic and metabolic transport between the lens cells. Gap junctions are specialization of the plasma membrane that connect adjacent cells to form low-resistance pathways that allow cells to share their ions and small metabolites. This form of intercellular communication is essential for a wide variety of biological processes including tissue homeostasis, cell differentiation and cell growth. The long term goal of this project is to understand the role of gap junctions in the development, maintenance and functioning of a mammalian lens. An objective of this project is to study the regulation of mouse gap junction protein genes. The lens gap junction proteins that will be studied will include the alpha 1(Cx43), alpha 3(Cx46) and alpha8(Cx50) connexins. Genomic clones that have been isolated for the alpha 1 alpha3 and alpha8 lens connexin genes will be characterized and the sequences involved in regulation of these genes during lens differentiation will be identified. A second objective is to determine the effect of dominant negative mutations on the interactions and functional expression of a3 and a8 connexin and will be analyzed using a mammalian cell culture system. These studies will further our understanding of regulation of other genes, other than crystallins, that are expressed in the lens. Furthermore, these studies will be important for potential use in future experiments involving targeting of dominant negative constructs to the lens. The resulting disruption of gap junctions and the consequences on lens development, differentiation and on expression of lens membrane proteins can then be analyzed.
| Nielsen, P A; Baruch, A; Giepmans, B N et al. (2001) Characterization of the association of connexins and ZO-1 in the lens. Cell Commun Adhes 8:213-7 |
| Baldo, G J; Gong, X; Martinez-Wittinghan, F J et al. (2001) Gap junctional coupling in lenses from alpha(8) connexin knockout mice. J Gen Physiol 118:447-56 |
| Benedetti, E L; Dunia, I; Recouvreur, M et al. (2000) Structural organization of gap junctions as revealed by freeze-fracture and SDS fracture-labeling. Eur J Cell Biol 79:575-82 |
| Gong, X; Baldo, G J; Kumar, N M et al. (1998) Gap junctional coupling in lenses lacking alpha3 connexin. Proc Natl Acad Sci U S A 95:15303-8 |
| Gong, X; Li, E; Klier, G et al. (1997) Disruption of alpha3 connexin gene leads to proteolysis and cataractogenesis in mice. Cell 91:833-43 |
