Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Exp Eye Res
2013 May 01;110:136-41. doi: 10.1016/j.exer.2012.10.010.
Show Gene links
Show Anatomy links
An MIP/AQP0 mutation with impaired trafficking and function underlies an autosomal dominant congenital lamellar cataract.
Senthil Kumar G
,
Kyle JW
,
Minogue PJ
,
Dinesh Kumar K
,
Vasantha K
,
Berthoud VM
,
Beyer EC
,
Santhiya ST
.
???displayArticle.abstract???
Autosomal dominant congenital cataracts have been associated with mutations of genes encoding several soluble and membrane proteins. By candidate gene screening, we identified a novel mutation in MIP (c.494 G > A) that segregates with a congenital lamellar cataract within a south Indian family and causes the replacement of a highly conserved glycine by aspartate (G165D) within aquaporin0 (AQP0). Unlike wild type AQP0, expression of AQP0-G165D in Xenopus oocytes did not facilitate swelling in hypotonic medium. In transfected HeLa cells, wild type AQP0 localized at the plasma membrane while AQP0-G165D was retained within the secretory pathway, and localized mainly within the endoplasmic reticulum. These results suggest that mutation of this conserved glycine residue leads to improper trafficking of AQP0-G165D and loss of water channel function. They emphasize the importance of AQP0 for maintenance of lens transparency and identify a critical residue that is conserved among aquaporins, but has not previously been associated with disease-associated replacement.
???displayArticle.pubmedLink???
23116563
???displayArticle.pmcLink???PMC3570674 ???displayArticle.link???Exp Eye Res ???displayArticle.grants???[+]
Al-Ghoul,
Lens structure in MIP-deficient mice.
2003, Pubmed
Al-Ghoul,
Lens structure in MIP-deficient mice.
2003,
Pubmed
Apple,
Elimination of cataract blindness: a global perspective entering the new millenium.
2000,
Pubmed
Engel,
Junction-forming aquaporins.
2008,
Pubmed
Francis,
Functional impairment of lens aquaporin in two families with dominantly inherited cataracts.
2000,
Pubmed
,
Xenbase
Gonen,
Aquaporin-0 membrane junctions reveal the structure of a closed water pore.
2004,
Pubmed
Gorelick,
Aquaporin-11: a channel protein lacking apparent transport function expressed in brain.
2006,
Pubmed
,
Xenbase
Gu,
A novel mutation in major intrinsic protein of the lens gene (MIP) underlies autosomal dominant cataract in a Chinese family.
2007,
Pubmed
Harries,
The channel architecture of aquaporin 0 at a 2.2-A resolution.
2004,
Pubmed
Hejtmancik,
Congenital cataracts and their molecular genetics.
2008,
Pubmed
Kalman,
AQP0-LTR of the Cat Fr mouse alters water permeability and calcium regulation of wild type AQP0.
2006,
Pubmed
,
Xenbase
Kyle,
An intact connexin N-terminus is required for function but not gap junction formation.
2008,
Pubmed
,
Xenbase
Loonen,
Aquaporin 2 mutations in nephrogenic diabetes insipidus.
2008,
Pubmed
Minogue,
An aberrant sequence in a connexin46 mutant underlies congenital cataracts.
2005,
Pubmed
,
Xenbase
Minogue,
A mutant connexin50 with enhanced hemichannel function leads to cell death.
2009,
Pubmed
,
Xenbase
Mulders,
Water channel properties of major intrinsic protein of lens.
1995,
Pubmed
,
Xenbase
Németh-Cahalan,
pH and calcium regulate the water permeability of aquaporin 0.
2000,
Pubmed
,
Xenbase
Németh-Cahalan,
Molecular basis of pH and Ca2+ regulation of aquaporin water permeability.
2004,
Pubmed
,
Xenbase
Puljung,
Polyvalent cations constitute the voltage gating particle in human connexin37 hemichannels.
2004,
Pubmed
,
Xenbase
Reneker,
Activation of unfolded protein response in transgenic mouse lenses.
2011,
Pubmed
Santhiya,
Molecular analysis of cataract families in India: new mutations in the CRYBB2 and GJA3 genes and rare polymorphisms.
2010,
Pubmed
Satin,
The cloned cardiac Na channel alpha-subunit expressed in Xenopus oocytes show gating and blocking properties of native channels.
1992,
Pubmed
,
Xenbase
Shiels,
Mutations in the founder of the MIP gene family underlie cataract development in the mouse.
1996,
Pubmed
Shiels,
Disruption of lens fiber cell architecture in mice expressing a chimeric AQP0-LTR protein.
2000,
Pubmed
Shiels,
Optical dysfunction of the crystalline lens in aquaporin-0-deficient mice.
2001,
Pubmed
Sorani,
Genetic variation in human aquaporins and effects on phenotypes of water homeostasis.
2008,
Pubmed
Varadaraj,
The role of MIP in lens fiber cell membrane transport.
1999,
Pubmed
Varadaraj,
Functional characterization of a human aquaporin 0 mutation that leads to a congenital dominant lens cataract.
2008,
Pubmed
,
Xenbase
Wang,
The impact of the unfolded protein response on human disease.
2012,
Pubmed
Zhou,
Major intrinsic protein (MIP) polymorphism is associated with age-related cataract in Chinese.
2011,
Pubmed
