Functional expression of aquaporins in embryonic, postnatal, and adult mouse lenses

Varadaraj, K.; Kumari, S. Sindhu; Mathias, Richard T.

doi:10.1002/dvdy.21125

Cited by 44 publications

(77 citation statements)

References 67 publications

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“…Mip transcripts and Mip protein were first detected at E11 in the differentiating primary fibre cells; its synthesis continued through the adult stage in the secondary fibre cells [85]. The human MIP gene is located on chromosome 12q13, and Berry et al [86] identified two dominant mutations (G134E and T138R) leading to polymorphic and lamellar cataract.…”

Section: Genes Causing Juvenile Cataractmentioning

confidence: 99%

Clinical and experimental advances in congenital and paediatric cataracts

Churchill

Graw

2011

Phil. Trans. R. Soc. B

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Cataracts (opacities of the lens) are frequent in the elderly, but rare in paediatric practice. Congenital cataracts (in industrialized countries) are mainly caused by mutations affecting lens development. Much of our knowledge about the underlying mechanisms of cataractogenesis has come from the genetic analysis of affected families: there are contributions from genes coding for transcription factors (such as FoxE3, Maf, Pitx3) and structural proteins such as crystallins or connexins. In addition, there are contributions from enzymes affecting sugar pathways (particularly the galactose pathway) and from a quite unexpected area: axon guidance molecules like ephrins and their receptors. Cataractous mouse lenses can be identified easily by visual inspection, and a remarkable number of mutant lines have now been characterized. Generally, most of the mouse mutants show a similar phenotype to their human counterparts; however, there are some remarkable differences. It should be noted that many mutations affect genes that are expressed not only in the lens, but also in tissues and organs outside the eye. There is increasing evidence for pleiotropic effects of these genes, and increasing consideration that cataracts may act as early and readily detectable biomarkers for a number of systemic syndromes.

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Section: Genes Causing Juvenile Cataractmentioning

confidence: 99%

Clinical and experimental advances in congenital and paediatric cataracts

Churchill

Graw

2011

Phil. Trans. R. Soc. B

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“…MIP/AQP0 water channels show different properties from those formed by AQP1 in either endogenous or exogenous functional assays. MIP/AQP0 water channels, besides functioning with lower efficiency than those formed by AQP1, are Hg 2+ -insensitive and pH-dependent, whereas AQP1 channels are inhibited by Hg 2+ and are pH-independent (Mulders et al 1995;Nemeth-Cahalan and Hall 2000;Varadaraj et al 1999Varadaraj et al , 2005Varadaraj et al , 2007.…”

Section: **mentioning

confidence: 97%

“…4a (Varadaraj et al 2005(Varadaraj et al , 2007. MIP/AQP0 water channels show different properties from those formed by AQP1 in either endogenous or exogenous functional assays.…”

Section: **mentioning

confidence: 98%

“…In the other functional assay, membrane vesicles formed from freshly isolated groups of lens fiber cells developed in Rick Mathias' laboratory have been used to study the function of the endogenous MIP/AQP0 expressed in the lens fibers of mouse, frog, and rabbit (Varadaraj et al 1999(Varadaraj et al , 2005(Varadaraj et al , 2007. As MIP/AQP0 is expressed only in the lens fibers whereas AQP1 is expressed in the lens epithelia (Hamann et al 1998;Stamer et al 1994;Varadaraj et al 2005Varadaraj et al , 2007, as shown in Fig …”

Section: Mip/aqp0 Functions As a Water Channel In The Lens Fibersmentioning

confidence: 99%

“…1 (Varadaraj et al 2007;Yancey et al 1988). Induction of differentiation of explanted lens epithelia into fibers by FGFs allows studying the activation of expression of the MIP gene during the differentiation of lens epithelia into fibers at the molecular level.…”

Section: Mip/aqp0 Gene Expression During Lens Differentiationmentioning

confidence: 99%

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Structural Function of MIP/Aquaporin 0 in the Eye Lens; Genetic Defects Lead to Congenital Inherited Cataracts

Chepelinsky

Handbook of Experimental Pharmacology

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Aquaporin 0 (AQP0) was originally characterized as a membrane intrinsic protein, specifically expressed in the lens fibers of the ocular lens and designated MIP, for major intrinsic protein of the lens. Once the gene was cloned, an internal repeat was identified, encoding for the amino acids Asp-Pro-Ala, the NPA repeat. Shortly, the MIP gene family was emerging, with members being characterized in mammals, insects, and plants. Once Peter Agre's laboratory developed a functional assay for water channels, the MIP family became the aquaporin family and MIP became known as aquaporin 0. Besides functioning as a water channel, aquaporin 0 also plays a structural role, being required for maintaining the transparency and optical accommodation of the ocular lens. Mutations in the AQP0 gene in human and mice result in genetic cataracts; deletion of the MIP/AQP0 gene in mice results in lack of suture formation required for maintenance of the lens fiber architecture, resulting in perturbed accommodation and focus properties of the ocular lens. Crystallography studies support the notion of the double function of aquaporin 0 as a water channel (open configuration) or adhesion molecule (closed configuration) in the ocular lens fibers. The functions of MIP/AQP0, both as a water channel and an adhesive molecule in the lens fibers, contribute to the narrow intercellular space of the lens fibers that is required for lens transparency and accommodation.

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A novel single‐base deletional mutation of MIP impairs protein distribution and cell‐to‐cell adhesion in autosomal dominant cataracts in a Chinese family

Yu,

Qiao,

et al. 2023

American J of Med Genetics Pt A

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Congenital cataracts are the leading cause of irreversible visual disability in children, and genetic factors play an important role in their development. In this study, targeted exome sequencing revealed a novel single‐base deletional mutation of MIP (c.301delG; p.Ala101Profs*16) segregated with congenital punctate cataract in a Chinese family. The hydrophobic properties, and secondary and tertiary structures for truncated MIP were predicted to affect the function of protein by bioinformatics analysis. When MIP‐WT and MIP‐Ala101fs expression constructs were singly transfected into HeLa cells, it was found that the mRNA level showed no significant difference, while the protein level of the mutant was remarkably reduced compared to that of the wild‐type MIP. Immunofluorescence images showed that the MIP‐WT was principally localized to the plasma membrane, whereas the MIP‐Ala101fs protein was aberrantly trapped in the cytoplasm. Furthermore, the cell‐to‐cell adhesion capability and the cell‐to‐cell communication property were both significantly reduced for MIP‐Ala101fs compared to the MIP‐WT (all *p < 0.05). This is the first report of the c.301delG mutation in the MIP gene associated with autosomal dominant congenital cataracts. We propose that the cataract is caused by the decreased protein expression and reduced cell‐to‐cell adhesion by the mutant MIP. The impaired trafficking or instability of the mutant protein, as well as compromised intercellular communication is probably a concurrent result of the mutation. The results expand the genetic and phenotypic spectra of MIP and help to better understand the molecular basis of congenital cataracts.

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Functional expression of aquaporins in embryonic, postnatal, and adult mouse lenses

Cited by 44 publications

References 67 publications

Clinical and experimental advances in congenital and paediatric cataracts

Clinical and experimental advances in congenital and paediatric cataracts

Structural Function of MIP/Aquaporin 0 in the Eye Lens; Genetic Defects Lead to Congenital Inherited Cataracts

A novel single‐base deletional mutation of MIP impairs protein distribution and cell‐to‐cell adhesion in autosomal dominant cataracts in a Chinese family

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