Dominant cataracts result from incongruous mixing of wild-type lens connexins
| Autor: | Leping Li, Xiaohua Gong, Caterina Sellitto, Francisco J. Martinez-Wittinghan, Richard T. Mathias, Thomas W. White, Peter R. Brink |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Heterozygote knockin knockover connexin lens intercellular communication Connexin Cell Communication Biology Cataract Connexins Ion Channels Article 03 medical and health sciences Mice 0302 clinical medicine Cataracts Crystallin Lens Crystalline medicine Animals Eye Proteins 030304 developmental biology Cell Size Fluorescent Dyes Genetics Mice Knockout 0303 health sciences Gap junction Wild type Gap Junctions Heterozygote advantage Cell Biology medicine.disease Crystallins Lens Fiber Cell biology Disease Models Animal Knockout mouse Mutation Female sense organs 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 0021-9525 |
| Popis: | Gap junctions are composed of proteins called connexins (Cx) and facilitate both ionic and biochemical modes of intercellular communication. In the lens, Cx46 and Cx50 provide the gap junctional coupling needed for homeostasis and growth. In mice, deletion of Cx46 produced severe cataracts, whereas knockout of Cx50 resulted in significantly reduced lens growth and milder cataracts. Genetic replacement of Cx50 with Cx46 by knockin rescued clarity but not growth. By mating knockin and knockout mice, we show that heterozygous replacement of Cx50 with Cx46 rescued growth but produced dominant cataracts that resulted from disruption of lens fiber morphology and crystallin precipitation. Impedance measurements revealed normal levels of ionic gap junctional coupling, whereas the passage of fluorescent dyes that mimic biochemical coupling was altered in heterozygous knockin lenses. In addition, double heterozygous knockout lenses retained normal growth and clarity, whereas knockover lenses, where native Cx46 was deleted and homozygously knocked into the Cx50 locus, displayed significantly deficient growth but maintained clarity. Together, these findings suggest that unique biochemical modes of gap junctional communication influence lens clarity and lens growth, and this biochemical coupling is modulated by the connexin composition of the gap junction channels. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|