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Targeted Ablation of Connexin50 in Mice Results in Microphthalmia and Zonular Pulverulent Cataracts

In the ocular lens, gap junctional communication is a key component of homeostatic mechanisms preventing cataract formation. Gap junctions in rodent lens fibers contain two known intercellular channel-forming proteins, connexin50 (Cx50) and Cx46. Since targeted ablation of Cx46 has been shown to cau...

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Autores principales: White, Thomas W., Goodenough, Daniel A., Paul, David L.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2148149/
https://www.ncbi.nlm.nih.gov/pubmed/9813099
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author White, Thomas W.
Goodenough, Daniel A.
Paul, David L.
author_facet White, Thomas W.
Goodenough, Daniel A.
Paul, David L.
author_sort White, Thomas W.
collection PubMed
description In the ocular lens, gap junctional communication is a key component of homeostatic mechanisms preventing cataract formation. Gap junctions in rodent lens fibers contain two known intercellular channel-forming proteins, connexin50 (Cx50) and Cx46. Since targeted ablation of Cx46 has been shown to cause senile-type nuclear opacities, it appears that Cx50 alone cannot meet homeostatic requirements. To determine if lens pathology arises from a reduction in levels of communication or the loss of a connexin-specific function, we have generated mice with a targeted deletion of the Cx50 gene. Cx50-null mice exhibited microphthalmia and nuclear cataracts. At postnatal day 14 (P14), Cx50-knockout eyes weighed 32% less than controls, whereas lens mass was reduced by 46%. Cx50-knockout lenses also developed zonular pulverulent cataracts, and lens abnormalities were detected by P7. Deletion of Cx50 did not alter the amounts or distributions of Cx46 or Cx43, a component of lens epithelial junctions. In addition, intercellular passage of tracers revealed the persistence of communication between all cell types in the Cx50-knockout lens. These results demonstrate that Cx50 is required not only for maintenance of lens transparency but also for normal eye growth. Furthermore, these data indicate that unique functional properties of both Cx46 and Cx50 are required for proper lens development.
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spelling pubmed-21481492008-05-01 Targeted Ablation of Connexin50 in Mice Results in Microphthalmia and Zonular Pulverulent Cataracts White, Thomas W. Goodenough, Daniel A. Paul, David L. J Cell Biol Regular Articles In the ocular lens, gap junctional communication is a key component of homeostatic mechanisms preventing cataract formation. Gap junctions in rodent lens fibers contain two known intercellular channel-forming proteins, connexin50 (Cx50) and Cx46. Since targeted ablation of Cx46 has been shown to cause senile-type nuclear opacities, it appears that Cx50 alone cannot meet homeostatic requirements. To determine if lens pathology arises from a reduction in levels of communication or the loss of a connexin-specific function, we have generated mice with a targeted deletion of the Cx50 gene. Cx50-null mice exhibited microphthalmia and nuclear cataracts. At postnatal day 14 (P14), Cx50-knockout eyes weighed 32% less than controls, whereas lens mass was reduced by 46%. Cx50-knockout lenses also developed zonular pulverulent cataracts, and lens abnormalities were detected by P7. Deletion of Cx50 did not alter the amounts or distributions of Cx46 or Cx43, a component of lens epithelial junctions. In addition, intercellular passage of tracers revealed the persistence of communication between all cell types in the Cx50-knockout lens. These results demonstrate that Cx50 is required not only for maintenance of lens transparency but also for normal eye growth. Furthermore, these data indicate that unique functional properties of both Cx46 and Cx50 are required for proper lens development. The Rockefeller University Press 1998-11-02 /pmc/articles/PMC2148149/ /pubmed/9813099 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Regular Articles
White, Thomas W.
Goodenough, Daniel A.
Paul, David L.
Targeted Ablation of Connexin50 in Mice Results in Microphthalmia and Zonular Pulverulent Cataracts
title Targeted Ablation of Connexin50 in Mice Results in Microphthalmia and Zonular Pulverulent Cataracts
title_full Targeted Ablation of Connexin50 in Mice Results in Microphthalmia and Zonular Pulverulent Cataracts
title_fullStr Targeted Ablation of Connexin50 in Mice Results in Microphthalmia and Zonular Pulverulent Cataracts
title_full_unstemmed Targeted Ablation of Connexin50 in Mice Results in Microphthalmia and Zonular Pulverulent Cataracts
title_short Targeted Ablation of Connexin50 in Mice Results in Microphthalmia and Zonular Pulverulent Cataracts
title_sort targeted ablation of connexin50 in mice results in microphthalmia and zonular pulverulent cataracts
topic Regular Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2148149/
https://www.ncbi.nlm.nih.gov/pubmed/9813099
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