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Exp Eye Res
2007 Mar 01;843:513-28. doi: 10.1016/j.exer.2006.11.004.
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Transgenic overexpression of connexin50 induces cataracts.
Chung J
,
Berthoud VM
,
Novak L
,
Zoltoski R
,
Heilbrunn B
,
Minogue PJ
,
Liu X
,
Ebihara L
,
Kuszak J
,
Beyer EC
.
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To examine the effects of increased expression of Cx50 in the mouse lens, transgenic mice were generated using a DNA construct containing the human Cx50 coding region and a C-terminal FLAG epitope driven by the chicken betaB1-crystallin promoter. Expression of this protein in paired Xenopus oocytes induced gap junctional currents of similar magnitude to wild type human Cx50. Three lines of transgenic mice expressing the transgenic protein were analyzed. Lenses from transgenic mice were smaller than those from non-transgenic littermates, and had cataracts that were already visible at postnatal day 1. Expression of the transgene resulted in a 3- to 13-fold increase in Cx50 protein levels above those of non-transgenic animals. Light microscopy revealed alterations in epithelial cell differentiation, fiber cell structure, interactions between fiber cells and areas of liquefaction. Scanning electron microscopy showed fiber cells of varying widths with bulging areas along single fibers. Anti-Cx50 and anti-FLAG immunoreactivities were detected at appositional membranes and in intracellular vesicles in transgenic lenses. N-cadherin, Cx46, ZO-1 and aquaporin 0 localized mainly at the plasma membrane, although some N-cadherin and aquaporin 0 was associated with the intracellular vesicles. The abundance and solubility/integrity of alphaA-, alphaB-, beta- and gamma-crystallin were unaffected. These results demonstrate that transgenic expression of Cx50 in mice leads to cataracts associated with formation of cytoplasmic vesicles containing Cx50 and decreased or slowed epithelial differentiation without major alterations in the distribution of other integral membrane or membrane-associated proteins or the integrity/solubility of crystallins.
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17217947
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Baldo,
Gap junctional coupling in lenses from alpha(8) connexin knockout mice.
2001, Pubmed
Baldo,
Gap junctional coupling in lenses from alpha(8) connexin knockout mice.
2001,
Pubmed
Barker,
Increased association of ZO-1 with connexin43 during remodeling of cardiac gap junctions.
2002,
Pubmed
Berthoud,
Heteromeric connexons formed by the lens connexins, connexin43 and connexin56.
2001,
Pubmed
Berthoud,
Loss of function and impaired degradation of a cataract-associated mutant connexin50.
2003,
Pubmed
Berthoud,
Highly restricted pattern of connexin36 expression in chick somite development.
2004,
Pubmed
Beyer,
Antisera directed against connexin43 peptides react with a 43-kD protein localized to gap junctions in myocardium and other tissues.
1989,
Pubmed
Bradford,
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
1976,
Pubmed
Brooks,
Ferritin crystal cataracts in hereditary hyperferritinemia cataract syndrome.
2002,
Pubmed
Cammarata,
A transgenic animal model of osmotic cataract. Part 1: over-expression of bovine Na+/myo-inositol cotransporter in lens fibers.
1999,
Pubmed
Capetanaki,
Overexpression of the vimentin gene in transgenic mice inhibits normal lens cell differentiation.
1989,
Pubmed
Chen,
Identification of supernumerary ring chromosome 1 mosaicism using fluorescence in situ hybridization.
1995,
Pubmed
Church,
The human lens intrinsic membrane protein MP70 (Cx50) gene: clonal analysis and chromosome mapping.
1995,
Pubmed
Duncan,
Chicken beta B1 crystallin: gene sequence and evidence for functional conservation of promoter activity between chicken and mouse.
1995,
Pubmed
Duncan,
Ectopic Pax6 expression disturbs lens fiber cell differentiation.
2004,
Pubmed
Dunia,
Plasma membrane-cytoskeleton damage in eye lenses of transgenic mice expressing desmin.
1990,
Pubmed
Ebihara,
Cloning and expression of a Xenopus embryonic gap junction protein.
1989,
Pubmed
,
Xenbase
Ebihara,
Xenopus connexin38 forms hemi-gap-junctional channels in the nonjunctional plasma membrane of Xenopus oocytes.
1996,
Pubmed
,
Xenbase
Finelli,
FISH characterization of a supernumerary r(1)(::cen-->q22::q22-->sq21::) chromosome associated with multiple anomalies and bilateral cataracts.
2001,
Pubmed
Giepmans,
The gap junction protein connexin43 interacts with the second PDZ domain of the zona occludens-1 protein.
,
Pubmed
Goldstein,
Cytosolic beta-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease.
2003,
Pubmed
Gong,
Disruption of alpha3 connexin gene leads to proteolysis and cataractogenesis in mice.
1997,
Pubmed
Gong,
Gap junctional coupling in lenses lacking alpha3 connexin.
1998,
Pubmed
Goodenough,
The crystalline lens. A system networked by gap junctional intercellular communication.
1992,
Pubmed
Gu,
Stimulation of lens cell differentiation by gap junction protein connexin 45.6.
2003,
Pubmed
Jiang,
Heteromeric connexons in lens gap junction channels.
1996,
Pubmed
,
Xenbase
Katar,
NCAM of the mammalian lens.
1993,
Pubmed
Kausalya,
Connexin45 directly binds to ZO-1 and localizes to the tight junction region in epithelial MDCK cells.
2001,
Pubmed
Laing,
Association with ZO-1 correlates with plasma membrane partitioning in truncated connexin45 mutants.
2005,
Pubmed
Laing,
Connexin45 interacts with zonula occludens-1 and connexin43 in osteoblastic cells.
2001,
Pubmed
Laing,
ZO-1 alters the plasma membrane localization and function of Cx43 in osteoblastic cells.
2005,
Pubmed
Mackay,
Connexin46 mutations in autosomal dominant congenital cataract.
1999,
Pubmed
Martin,
Lens-specific expression of a major histocompatibility complex class I molecule disrupts normal lens development and induces cataracts in transgenic mice.
1995,
Pubmed
Musil,
Expression of the gap junction protein connexin43 in embryonic chick lens: molecular cloning, ultrastructural localization, and post-translational phosphorylation.
1990,
Pubmed
Nielsen,
Lens connexins alpha3Cx46 and alpha8Cx50 interact with zonula occludens protein-1 (ZO-1).
2003,
Pubmed
Paul,
Connexin46, a novel lens gap junction protein, induces voltage-gated currents in nonjunctional plasma membrane of Xenopus oocytes.
1991,
Pubmed
,
Xenbase
Perez-Castro,
Defective lens fiber differentiation and pancreatic tumorigenesis caused by ectopic expression of the cellular retinoic acid-binding protein I.
1993,
Pubmed
Roth,
Chicken beta B1-crystallin gene expression: presence of conserved functional polyomavirus enhancer-like and octamer binding-like promoter elements found in non-lens genes.
1991,
Pubmed
Segretain,
A proposed role for ZO-1 in targeting connexin 43 gap junctions to the endocytic pathway.
2004,
Pubmed
Sellitto,
Connexin50 is essential for normal postnatal lens cell proliferation.
2004,
Pubmed
Shiels,
Optical dysfunction of the crystalline lens in aquaporin-0-deficient mice.
2001,
Pubmed
Shiels,
A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant "zonular pulverulent" cataract, on chromosome 1q.
1998,
Pubmed
Singh,
Connexin 43 interacts with zona occludens-1 and -2 proteins in a cell cycle stage-specific manner.
2005,
Pubmed
Sivak,
The interrelationship of lens anatomy and optical quality. I. Non-primate lenses.
1994,
Pubmed
Spray,
Equilibrium properties of a voltage-dependent junctional conductance.
1981,
Pubmed
,
Xenbase
Steele,
A mutation in the connexin 50 (Cx50) gene is a candidate for the No2 mouse cataract.
1998,
Pubmed
Toyofuku,
Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac myocytes.
1998,
Pubmed
West-Mays,
Ectopic expression of AP-2alpha transcription factor in the lens disrupts fiber cell differentiation.
2002,
Pubmed
White,
Unique and redundant connexin contributions to lens development.
2002,
Pubmed
White,
Targeted ablation of connexin50 in mice results in microphthalmia and zonular pulverulent cataracts.
1998,
Pubmed
White,
Mouse Cx50, a functional member of the connexin family of gap junction proteins, is the lens fiber protein MP70.
1992,
Pubmed
,
Xenbase
Wu,
Role of catenins in the development of gap junctions in rat cardiomyocytes.
2003,
Pubmed
Yu,
Interaction of major intrinsic protein (aquaporin-0) with fiber connexins in lens development.
2004,
Pubmed
Zillig,
Overexpression and properties of wild-type and Tyr437His mutated myocilin in the eyes of transgenic mice.
2005,
Pubmed
