Abstract
Much of our knowledge about the function of genes in cataracts has been derived from the molecular analysis of spontaneous or induced mutations in the mouse. Mutations affecting the mouse lens can be identified easily by visual inspection, and a remarkable number of mutant lines have been characterized. In contrast to humans, most of the genetic mouse cataract models suffer from congenital cataracts, and only a few develop cataracts in old age. Therefore, the mouse cataract models contributed rather to the understanding of lens development than to the ageing process taking place in the lens. A prerequisite formolecular analysis is the chromosomal localization of the gene. In this review, several mouse models will be discussed with emphasis on the underlying genetic basis rather than the morphological features as exemplified by the following: (i) the most frequent mutations in congenital cataracts affect genes coding for γ-crystallins (gene symbol: Cryg); (ii) some postnatal, progressive cataracts have been characterized by mutations in the β-crystallin encoding genes (Cryb); (iii) mutations in genes coding for membrane proteins like MIP or connexins lead to congenital cataracts; (iv) mutations in genes coding for transcription factors such as FoxE3, Maf, Sox1, and Six5 cause cataracts; (v) mouse models suffering from hereditary age-related cataracts (e.g. Emory cataract) have not yet been characterized genetically. In conclusion, a broad variety of hereditary congenital cataracts are well understood at the molecular level. Further, expression patterns of the affected genes in several other tissues and organs outside the eye, is making it increasingly clear that isolated cataracts are the exception rather than the rule. By further understanding the pleiotropic effects of these genes, we might recognize cataracts as an easily visible biomarker for a number of systemic syndromes.
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Ai Y., Zheng Z., O’Brien-Jenkins A., Bernard D. J., Wynshaw-Boris T., Ning C. et al. 2000 A mouse model of galactose-induced cataracts. Hum. Mol. Genet. 12, 1821–1827.
Ainsbury E. A., Bouffler S. D., Dörr W., Graw J., Muirhead C. R., Edwards A. A. and Cooper J. 2009 Radiation cataractogenesis: a review of recent studies. Radiat. Res. 172, 1–9.
Alizadeh A., Clark J. I., Seeberger T., Hess J., Blankenship T., Spicer A. and FitzGerald P. G. 2002 Targeted genomic deletion of the lens-specific intermediate filament protein CP49. Invest. Ophthalmol. Vis. Sci. 43, 3722–3727.
Alizadeh A., Clark J., Seeberger T., Hess J., Blankenship T. and FitzGerald P. G. 2003 Targeted deletion of the lens fibre cellspecific intermediate filament protein filensin. Invest. Ophthalmol. Vis. Sci. 44, 5252–5258.
Ardayfio P., Moon J., Leung K. K., Youn-Hwang D. and Kim K. S. 2008 Impaired learning and memory in Pitx3 deficient aphakia mice: a genetic model for striatum-dependent cognitive symptoms in Parkinsons disease. Neurobiol. Dis. 31, 406–412.
Barbaric I., Wells S., Russ A. and Dear T. N. 2007 Spectrum of ENU-induced mutations in phenotype-driven and gene-driven screens in the mouse. Environ. Mol. Mutagen. 48, 124–142.
Baruch A., Greenbaum D., Levy E. T., Nielsen P. A., Gilula N. B., Kumar N. M. and Bogyo M. 2001 Defining a link between jap junction communication, proteolysis, and cataract formation. J. Biol. Chem. 276, 28999–29006.
Bayle J. H., Randazzo F., Johnen G., Kaufman S., Nagy A., Rossant J. and Crabtree G. R. 2002 Hyperphenylalaninemia and impaired glucose tolerance in mice lacking the bifunctional DCoH gene. J. Biol. Chem. 277, 28884–28891.
Berry V., Mackay D., Khaliq S., Francis P. J., Hameed A., Anwar K. et al. 1999 Connexin 50 mutation in a family with congenital zonular nuclear pulverulent cataract of Pakistani origin. Hum. Genet. 105, 168–170.
Blixt A., Mahlapuu M., Aitola M., Pelto-Huikko M., Enerbäck S. and Carlsson P. 2000 A forkhead gene, FoxE3, is essential for lens epithelial proliferation and closure of the lens vesicle. Genes Dev. 14, 245–254.
Brady J. P., Garland D., Duglass-Tabor Y., Robison Jr W. G., Groome A. and Wawrousek E. F. 1997 Targeted disruption of the mouse αA-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein αBcrystallin. Proc. Natl. Acad. Sci. USA 94, 884–889
Brady J. P., Garland D. L., Green D. E., Tamm E. R., Giblin F. J. and Wawrousek E. F. 2001 αB-crystallin in lens development and muscle integrity: a gene knockout approach. Invest. Ophthalmol. Vis. Sci. 42, 2924–2934.
Brakenhoff R. H., Aarts H. J. M., Reek F. H., Lubsen N. H. and Schoenmakers J. G. G. 1990 Human γ-crystallin gene — a gene family on its way to extinction. J. Mol. Biol. 216, 519–532.
Bu L., Jin Y., Shi Y., Chu R., Ban A., Eiberg H. et al. 2002 Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataract. Nat. Genet. 31, 276–278.
Bu L., Yan S., Jin M., Jin Y., Yu C., Xiao S. et al. 2002 The γS-crystallin gene is mutated in autosomal recessive cataract in mouse. Genomics 80, 38–44.
Cartier M., Breitman M. L. and Tsui L. C. 1992 A frameshift mutation in the γE-crystallin gene of the Elo mouse. Nat. Genet. 2, 42–45.
Chambers C. and Russell P. 1991 Deletion mutation in an eye lens β-crystallin. J. Biol. Chem. 266, 6742–6746.
Chan A. W. H., Ho Y.-S., Chung S. K. and Chung S. S. M. 2008 Synergistic effect of osmotic and oxidative stress in slowdeveloping cataract formation. Exp. Eye Res. 87, 454–461.
Chang B., Hawes N. L., Roderick T. H., Smith R. S., Heckenlively J. R., Horwitz J. and Davisson M. T. 1999 Identification of a missense mutation in the αA-crystallin gene of the lop18 mouse. Mol. Vis. 5, 21.
Chang B., Wang X., Hawes N. L., Ojakian R., Davisson M. T., Lo W. K. and Gong X. 2002 A Gja8 (Cx50) point mutation causes an alteration of α3 connexin (Cx46) in semi-dominant catatacts of Lop10 mice. Hum. Mol. Genet. 11, 507–513.
Chepelinsky A. B. 2009 Structural function of MIP/Aquaporin 0 in the eye lens; genetic defects lead to congenital inherited cataracts. In Aquaporins (ed. E. Beitz). Handb. Exp. Pharmacol. 190, 265–297.
Cheong C., Sung, Y. H., Lee J., Choi Y. S., Song J., Kee C. and Lee H. W. 2006 Role of INK4a locus in normal eye development and cataract genetics. Mech. Ageing Dev. 127, 633–638.
Clark A. T., Goldowitz D., Takahashi J. S., Vitaterna M. H., Siepka S. M., Peters L. L. et al. 2004 Implementing large-scale ENU mutagenesis screens in North America. Genetica 122, 51–64.
Conley Y. P., Erturk D., Keverline A., Mah T. S., Keravala A., Barnes L. R. et al. 2000 A juvenile-onset, progressive cataract locus on chromosome 3q21q22 is associated with a missense mutation in the beaded filament structural protein-2. Am. J. Hum. Genet. 66, 1426–1431.
Cooper M. A., Son A. I., Komlos D., Sun Y., Kleiman N. J. and Zhou R. 2008 Loss of ephrin-A5 function disrupts lens fibre cell packing and leads to cataract. Proc. Natl. Acad. Sci. USA 105, 16620–16625.
Cooper M. A., Kobayashi K. and Zhou R. 2009 Ephrin-A5 regulates the formation of the ascending midbrain dopaminergic pathways. Develop. Neurobiol. 69, 36–46.
Dahl K., Buschard K., Gram D. X., dApice A. J. F. and Hansen A. K. 2006 Glucose intolerance in a xenotransplantation model: studies in alpha-gal knockout mice. APMIS 114, 805–811.
Dahm R., van Marle J., Prescott A. R. and Quinlan R. A. 1999 Gap junctions containing α8-connexin (MP70) in the adult mammalian lens epithelium suggests a re-evaluation of its role in the lens. Exp. Eye Res. 69, 45–56.
Davis L. K., Meyer K. J., Rudd D. S., Librant A. L., Epping E. A., Sheffield V. C. and Wassink T. H. 2008 Pax6 3 deletion results in aniridia, autism and mental retardation. Hum. Genet. 123, 371–378.
DeRosa A. M., Xia C. H., Gong X. and White T. W. 2007 The cataract-inducing S50P mutation in Cx50 dominantly alters the channel gating of wild-type lens connexins. J. Cell Sci. 120, 4107–4116.
Devi R. R., Yao W., Vijayalakshmi P., Sergeev Y. V., Sundaresan P. and Hejtmancik J. F. 2008 Crystallin gene mutations in Indian families with inherited pediatric cataract. Mol. Vis. 14, 1157–1170.
DuPrey K. M., Robinson K. M., Wang Y., Taube J. R. and Duncan M. K. 2007 Subfertility in mice harboring a mutation in βB2-crystallin. Mol. Vis. 13, 366–373.
Ehling U. H., Charles D. J., Favor J., Graw J., Kratochvilova J., Neuhäuser-Klaus A. and Pretsch W. 1985 Induction of gene mutations in mice: the multiple endpoint approach. Mutat. Res. 150, 393–401.
Everett C. A., Glenister P. H., Taylor D. M., Lyon M. F., Kratochvilova-Löster J. and Favor J. 1994 Mapping of six dominant cataract genes in the mouse. Genomics 20, 429–434.
Favor J. 1984 Characterization of dominant cataract mutations in mice: penetrance, fertility and homozygous viability of mutations recovered after 250 mg/kg ethylnitrosourea paternal treatment. Genet. Res. 44, 183–197.
Favor J., Grimes P., Neuhäuser-Klaus A., Pretsch W. and Stambolian D. 1997 The mouse Cat4 locus maps to chromosome 8 and mutants express lens-corneal adhesion. Mamm. Genome 8, 403–406.
Favor J., Gloeckner C. J., Neuhäuser-Klaus A., Pretsch W., Sandulache R., Saule S. and Zaus I. 2008 Relationship of Pax6 activity levels to the extent of eye development in the mouse, Mus musculus. Genetics 179, 1345–1355.
Forshew T., Johnson C. A., Khaliq S., Pasha S., Willis C., Abbasi R. et al. 2005 Locus heterogeneity in autosomal recessive congenital cataracts: linkage to 9q and germline HSF4 mutations. Hum. Genet. 117, 452–459.
Fraser F. C. and Schabtach G. 1962 ’shrivelled’: a hereditary degeneration of the lens in the house mouse. Genet. Res. 3, 383–387.
Fritz A., Walch A., Piotrowska K., Roseman M., Schäffer E., Weber K. et al. 2002 Recessive transmission of a multiple endocrine neoplasia syndrome in the rat. Cancer Res. 62, 3048–3051.
Ganguly K., Favor J., Neuhäuser-Klaus A., Sandulache R., Puk O., Beckers J. et al. 2008 Novel allele of Crybb2 in the mouse and its expression in the brain. Invest. Ophthalmol. Vis. Sci. 49, 1533–1541.
Gao Y. and Spray D. C. 1998 Structural changes in lenses of mice lacking the gap junction protein connexin43. Invest. Ophthalmol. Vis. Sci. 39, 1198–1209.
Gong X., Li E., Klier G., Huang Q., Wu Y., Lei H. et al. 1997 Disruption of α3 connexin gene leads to proteolysis and cataractogenesis in mice. Cell 91, 833–843.
Gong X., Agopian K., Kumar N. M., and Gilula N. B. 1999 Genetic factors influence cataract formation in α3 connexin knockout mice. Dev. Genet. 24, 27–32.
Graw J. 2003 The genetic and molecular basis of congenital eye defects. Nat. Rev. Genet. 4, 877–888.
Graw J. 2004 Congenital hereditary cataracts. Int. J. Dev. Biol. 48, 1031–1044
Graw J. 2009 Genetics of crystallins: Cataract and beyond. Exp. Eye Res. 88, 173–189.
Graw J., Kratochvilova J. and Summer K.-H. 1984 Genetical and biochemical studies of a dominant cataract mutant in mice. Exp. Eye Res. 39, 37–45.
Graw J. and Liebstein A. 1993 DNase activity in murine lenses: implications for cataractogenesis. Graefe’s Arch. Clin. Exp. Ophthalmol. 231, 354–358.
Graw J., Reitmeir P. and Wulff A. 1990a Osmotic state of lenses in three dominant murine cataract mutants. Graefe’s Arch. Clin. Exp. Ophthalmol. 228, 252–254.
Graw J., Werner T., Merkle S., Reitmaier P., Schäffer E. and Wulff A. 1990b Histological and biochemical characterization of the murine cataract mutant Nop. Exp. Eye Res. 50, 449–456.
Graw J., Löster J., Soewarto D., Fuchs H., Meyer B., Reis A. et al. 2001a Characterization of a new, dominant V124E mutation in the mouse αA-crystallin-encoding gene. Invest. Ophthalmol. Vis. Sci. 42, 2909–2913
Graw J., Löster J., Soewarto D., Fuchs H., Meyer B., Reis A. et al. 2001b Characterization of a mutation in the lens-specific MP70 encoding gene of the mouse leading to a dominant cataract. Exp. Eye Res. 73, 867–876.
Graw J., Löster J., Soewarto D., Fuchs H., Reis A., Wolf E. et al. 2001c Aey2, a new mutation in the βB2-crystallin-encoding gene in the mouse. Invest. Ophthalmol. Vis. Sci. 42, 1574–1580
Graw J., Neuhäuser-Klaus A., Klopp N., Selby P. B., Löster J. and Favor J. 2004 Genetic and allelic heterogeneity of Cryg mutations in eight distinct forms of dominant cataract in the mouse. Invest. Ophthalmol. Vis. Sci. 45, 1202–1213
Grimes P. A., Koeberlein B., Favor J., Neuhäuser-Klaus A. and Stambolian D. 1998 Abnormal development associated with Cat4a, a dominant mouse cataract mutation on chromosome 8. Invest. Ophthalmol. Vis. Sci. 39, 1863–1869.
Hammond C. J., Snieder H., Spector T. D. and Gilbert C. E. 2000 Genetic and environmental factors in age-related nuclear cataracts in monozygotic and dizygotic twins. N. Engl. J. Med. 342, 1786–1790.
Hammond C. J., Duncan D. D., Snieder H., de Lange M., West S. K., Spector T. D. and Gilbert C. E. 2001 The heritability of agerelated cortical cataract: the twin eye study. Invest. Ophthalmol. Vis. Sci. 42, 601–605.
Hansen L., Mikkelsen A., Nürnbereg P., Nürnberg G., Anjum I., Eiberg H. and Rosenberg T. 2009. Comprehensive mutational screening in a cohort of Danish families with hereditary congenital cataract. Invest. Ophthalmol. Vis. Sci. 50, 3291–3303.
Hill R. E., Favor J., Hogan B. L. M., Ton C. C. T., Saunders G. F., Hanson I. M. et al. 1991 Mouse Small eye results from mutations in a paired-like homeobox-containing gene. Nature 354, 522–525
Hong H. K., Lass J. H. and Chakravarti A. 1999 Pleiotropic skeletal and ocular phenotypes of the mouse mutation congenital hydrocephalus (ch/Mf1) arise frome a winged helix/forkhead transcription factor gene. Hum. Mol. Genet. 8, 625–637.
Hrabé de Angelis M., Flaswinkel H., Fuchs H., Rathkolb B., Soewarto D et al. 2000 Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nat. Genet. 25, 1–4.
Huang K. M., Wu J., Duncan M. K., Moy C., Dutra A., Favor J. et al. 2006 Xcat, a novel mouse model for NanceHoran syndrome inhibits expression of the cytoplasmic-targeted Nhs1 isoform. Hum. Mol. Genet. 15, 319–327.
Hwang D.-Y., Ardayfio P., Kang U. J., Semina E. V. and Kim K.-S. 2003 Selective loss of dopaminergic neurons in the substantia nigra of Pitx3-deficient aphakia mice. Mol. Brain Res. 114, 123–131.
Jakobs P. M., Hess J. F., FitzGerald P. G., Kramer P., Weleber R. G. and Litt M. 2000 Autosomal-dominant congenital cataract associated with a deletion mutation in the human beaded filament protein BFSP2. Am. J. Hum. Genet. 66, 1432–1436.
Jamieson R. V., Perveen R., Kerr B., Carette M., Yardley J., Héon E. et al. 2002 Domain disruption and mutation of the bZIP transcription factor, MAF, associated with cataract, ocular anterior segment dysgenesis and coloboma. Hum. Mol. Genet. 11, 33–42.
Jiang J. X., White T. W. and Goodenough D. A. 1995 Changes in connexin expression and distribution during chick lens development. Dev. Biol. 168, 649–661.
Johnson G. J. and Foster A. 2004 Prevalence, incidence and distribution of visual impairment. In The epidemiology of eye disease (ed. G. J. Johnson, D. C. Minassian, R. A. Weale and S. K. West), pp. 3–28. Arnold, London, UK.
Jun G., Guo H., Klein B. E. K., Klein R., Wang J. J., Mitchell P. et al. 2009 EPHA2 is associated with age-related cortical cataract in mice and humans. PLoS Genet. 5, e1000584.
Kamachi Y., Uchikawa M., Collignon J., Lovell-Badge R. and Kondoh H. 1998 Involvement of Sox1, 2 and 3 in the early and subsequent molecular events of lens induction. Development 125, 2521–2532.
Kamachi Y., Uchikawa M. and Kondoh H. 2000 Pairing SOX off with partners in the regulation of embryonic development. Trends Genet. 16, 182–187.
Ke T., Wang Q. K., Ji B., Wang X., Liu P., Zhang X. et al. 2006 Novel HSF4 mutation causes congenital total white cataract in a Chinese family. Am. J. Ophthalmol. 142, 298–303.
Kerscher S., Glennister P. H., Favor J. and Lyon M. F. 1996 Two new cataract loci, Ccw and To3, and further mapping of the Npp and Opj cataracts in the mouse. Genomics 36, 17–21.
Khan A. O., Aldahmesh M. A. and Meyer B. 2007 Recessive congenital total cataract with microcornea and heterozygote carrier signs caused by a novel missense CRYAA mutation (R54C). Am. J. Ophthalmol. 144, 949–952.
Klopp N., Favor J., Löster J., Lutz R. B., Neuhäuser-Klaus A., Prescott A. et al. 1998 Three murine cataract mutants (Cat2) are defective in different ?-crystallin genes. Genomics 52, 152–158
Koopman P. 1999 Sry and Sox9: mammalian testis-determining genes. Cell. Mol. Life Sci. 55, 839–856.
Kratochvilova J. and Ehling U. H. 1979 Dominant cataract mutations induced by γ-irradiation of male mice. Mutat. Res. 63, 221–223.
Kuck J. F. R. 1990 Late onset hereditary cataract of the Emory mouse: a model for human senile cataract. Exp. Eye Res. 50, 659–664.
Kuck J. F. R., Kuwabara T. and Kuck K. D. 1981 The Emory mouse cataract: an animal model for human senile cataract. Curr. Eye Res. 1, 643–649.
Kuwabara T. and Imaizumi M. 1974 Denucleation process of the lens. Invest. Ophthalmol. 13, 973–981.
Liedtke T., Schwamborn J. C., Schröer U. and Thanos S. 2007. Elongation of axons during regeneration involves retinal crystallin b2 (crybb2). Mol. Cell. Prot. 6, 895–907.
Liu X. Y., Dangel A.W., Kelley R. I., Zhao W., Denny P., Botcherby M. et al. 1999 The gene mutated in bare patches and sdtriated mice encodes a novel 3β-hydroxysteroid dehydrogenase. Nat. Genet. 22, 182–187.
Lyon M. F., Jarvis S. E., Sayers I. and Holmes R. S. 1981 Lens opacity: a new gene for congenital cataract on chromosome 10 of the mouse. Genet. Res. 38, 337–341.
Lyon M. F., Jamieson R. V., Perveen R., Glenister P. H., Griffiths R., Boyd Y. et al. 2003 A dominant mutation within the DNA-binding domain of the bZIP transcription factor Maf causes murine cataract and results in selective alteration in DNA binding. Hum. Mol. Genet. 12, 585–594.
Magabo K. S., Horwitz J., Piatigorsky J and Kantorow M. 2000 Expression of βB2-crystallin mRNA and protein in retina, brain and testis. Invest. Ophthalmol. Vis. Sci. 41, 3056–3060.
Mansergh F. C., Wride M. A., Walker V. E., Adams, S., Hunter S. M. and Evans M. J. 2004 Gene expression changes during cataract progression in Sparc null mice: Differential regulation of mouse globins in the lens. Mol. Vis. 10, 490–511.
Matsuo T., Osumi-Yamashita N., Noji S., Ohuchi H., Koyama E., Myokai F. et al. 1993 A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells. Nat. Genet. 3, 229–304.
Moré M. I., Kirsch F. P. and Rathjen F. G. 2001 Targeted ablation of NrCAM or ankyrin-B results in disorganized lens fibres leading to cataract formation. J. Cell Biol. 154, 187–196.
Moseley A., Graw J. and Delamere N. A. 2002 Altered Na, KATPase pattern in γ-crystallin mutant mice. Invest. Ophthalmol. Vis. Sci. 43, 1517–1519.
Mou L., Xu J. Y., Li W., Lei X., Wu Y., Xu G. et al. 2009 Identification of vimentin as a novel target of HSF4 in lens development and cataract by proteomic analysis. Invest. Ophthalmol. Vis. Sci. (in press).
Muggleton-Harris A. L., Festing M. F.W. and Hall M. 1987 A gene location for the inheritance of the cataract Fraser (CatFr) mouse congenital cataract. Genet. Res. 49, 235–238.
Nishiguchi S., Wood H., Kondoh H., Lovell-Badge R. and Episkopou V. 1998 Sox1 directly regulates the γ-crystallin gene and is essential for lens development in mice. Genes Dev. 12, 776–781.
Nishimoto H., Uga S., Miyata M., Ishikawa S. and Yamashita K. 1993 Morphological study of the cataractous lens of the senescence accelerated mouse. Graefe’s Arch. Clin. Exp. Ophthalmol. 231, 722–728
Nishimura D. Y., Searby C. C., Alward W. L., Walton D., Craig J. E., Mackey D. A. et al. 2001 A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for developmental defects of the anterior chamber of the eye. Am. J. Hum. Genet. 68, 364–372.
Nishizawa M., Kataoka K., Goto N., Fujiwara K. T. and Kawai S. 1989 v-maf, a viral oncogene that encodes a ‘leucine zipper’ motif. Proc. Natl. Acad. Sci. USA 86, 7711–7715.
Norose K., Clark J. I., Syed N. A., Basu A., Heber-Katz E., Sage E. H. and Howe C. C. 1998 SPARC deficiency leads to early-onset cataractogenesis. Invest. Ophthalmol. Vis. Sci. 39, 2674–2680.
Nunes I., Tovmasian L. T., Silva R. M., Burke R. E. and Goff S. P. 2003 Pitx3 is required for development of substantia nigra dopam inergic neurons. Proc. Natl. Acad. Sci. USA 100, 4245–4250.
Ogino H. and Yasuda K. 1998 Induction of lens diffedrentiation by activation of a bZIP transcription factor, L-Maf. Science 280, 115–118.
Okamura T., Miyoshi I., Takahashi K., Mototani Y., Ishigaki S., Kon Y. and Kasai N. 2003 Bilateral congenital cataracts result from a gain-of-function mutation in the gene for aquaporin-0 in mice. Genomics 81, 361–368.
Okano Y., Asada M., Fujimoto A., Ohtake A., Murayama K., Hsiao K. J. et al. 2001 A genetic factor for age-related cataract: Identification and characterization of a novel galactokinase variant, ‘Osaka,’ in Asians. Am. J. Hum. Genet. 68, 1036–1042.
Pellegata N. S., Quintanilla-Martinez L., Siggelkow H., Samson E., Bink K., Höfler H. et al. 2006 Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc. Natl. Acad. Sci. USA 103, 15558–15563.
Perveen R., Favor J., Jamieson R. V., Ray D. W. and Black G. C. M. 2007 A heterozygous c-Maf transactivation domain mutation causes congenital cataract and enhances target gene activation. Hum. Mol. Genet. 16, 1030–1038.
Ponnam S. P. G., Ramesha K., Tejwani S., Matalia J. and Kannabiran C. 2008 A missense mutation in LIM2 causes autosomal recessive congenital cataract. Mol. Vis. 14, 1204–1208.
Pras E., Frydman M., Levy-Nisserbaum E., Bakhan T., Raz J., Assia E. I. et al. 2000 A nonsense mutation (W9x) in CRYAA causes autosomal recessive cataract in an inbred Jewish Persian family. Invest. Ophthalmol. Vis. Sci. 41, 3511–3575.
Pras E., Levy-Nissenbaum E., Bakhan T., Lahat H., Assia E., Geffen-Carmi N. et al. 2002 A missense mutation in the LIM2 gene is associated with autosomal recessive presenile cataract in an inbred Iraqi Jewish family. Am. J. Hum. Genet. 70, 1363–1367.
Puk O., Löster J., Dalke C., Soewarto D., Fuchs H., Budde B. et al. 2008 Mutation in a novel connexin-like gene (Gjf1) in the mouse affects early lens development and causes a variable small-eye phenotype. Invest. Ophthalmol. Vis. Sci. 49, 1525–1532.
Ramachandran R. D., Perumalsamy V. and Hejtmancik J. F. 2007 Autosomal recessive juvenile onset cataract associated with mutation in BFSP1. Hum. Genet. 121, 475–482.
Reaume A. G., de Sousa P. A., Kulkarni S., Langille B. L., Zhu D., Davies T. C. et al. 1995 Cardiac malformation in neonatal mice lacking connexin43. Science 267, 1831–1834.
Rieger D. K., Reichenberger E., McLean W., Sidow A. and Olsen B. R. 2001 A double-deletion mutation in the Pitx3 gene causes arrested lens deveopment in aphakia mice. Genomics 72, 61–72.
Ring B. Z., Cordes S. P., Overbeek P. A. and Barsh G. S. 2000 Regulation of mouse lens fibre cell development and differentiation by the Maf gene. Development 127, 307–317.
Robinson M. L. and Overbeek P. A. 1996 Differential expression of αA- and αB-crystallins during murine ocular development. Invest. Ophthalmol. Vis. Sci. 37, 2276–2284
Rossi M., Morita H., Sormunen R., Airenne S., Kreivi M., Wang L. et al. 2003 Heparan sulfate chains of perlecan are indispensable in the lens capsule but not in the kidney. EMBO J. 22, 236–245.
Sajjad N., Goebel I., Kakar N., Cheema A. M., Kubisch C. and Ahmad J. 2008 A novel HSF4 gene mutation (p.R405X) causing autosomal recessive congenital cataracts in a large consanguineous family from Pakistan. BMC Med. Genet. 9, 99 (doi:10.1186/147I-2350-9-99).
Sandilands A., Hutcheson A. M., Long H. A., Prescott A. R., Vrensen G., Löster J. et al. 2002 Altered aggregation properties of mutant γ-crystallins cause inherited cataract. EMBO J. 21, 6005–6014
Sandilands A., Prescott A. R., Wegener A., Zoltoski R. K., Hutcheson A.M., Masaki S. et al. A. 2003 Knockout of the intermediate filament protein CP49 destabilises the lens fibre cytoskeleton and decreases lens optical quality, but does not induce cataract. Exp. Eye Res. 76, 385–391.
Sandilands A., Wang X., Hutcheson A. M., James J., Prescott A. R., Wegener A. et al. 2004 Bfsp2 mutation found in mouse 129 strains causes the loss of CP49 and induces vimentin-dependent changes in the lens fibre cell cytoskeleton. Exp. Eye Res. 78, 875–889.
Sarkar P. S., Appukuttan B., Han J., Ito Y., Ai C., Tsai W. et al. 2000 Heterozygous loss of Six5 in mice is sufficient to cause ocular cataracts. Nat. Genet. 25, 110–114.
Semina E. V., Ferrell R. E., Mintz-Hittner H. A., Bitoun P., Alward W. L. M., Reiter R. S. et al. 1998 A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD. Nat. Genet. 19, 167–170.
Semina E., Murray J. C., Reiter R., Hrstka R. F. and Graw J. 2000 Deletion in the promoter region and altered expression of Pitx3 homeobox gene in aphakia mice. Hum. Mol. Genet. 9, 1575–1585.
Semina E. V., Brownell I., Mintz-Hittner H. A., Murray J. C. and Jamrich M. 2001 Mutations in the human forkhead transcription factor FOXE3 associated with anterior segment ocular dysgenesis and cataracts. Hum. Mol. Genet. 10, 231–236.
Sheets N. L., Chauhan B. K., Wawrousek E., Hejtmancik J. F., Cvekl A. and Kantorow M. 2002 Cataract- and lens-specific upregulation of ARK receptor tyrosine kinase in Emory mouse cataract. Invest. Ophthalmol. Vis. Sci. 43, 1870–1875.
Shi Y., Shi X., Jin Y., Miao A., Bu L., He J. et al. 2008 Mutation screening of HSF4 in ISO age-related cataract patients Mol. Vis. 14, 1850–1855.
Smaoui N., Beltaief O., BenHamed S., MRad R., Maazoul F., Ouertani A. et al. 2004 A homozygous splice mutation in the HSF4 gene is associated with an autosomal recessive congenital cataract. Invest. Ophthalmol. Vis. Sci. 45, 2716–2721. Shi X., Cui B., Wang Z., Weng L., Xu Z., Ma J. et al. 2009 Removal of Hsf4 leads to cataract development in mice through down-regulation of γS-crystallin and Bfsp expression. BMC Mol. Biol. 10 (doi: 10.1186/1471-2199-10-10).
Shiels A. and Griffin C. S. 1993 Aberrant expression of the gene for lens major intrinsic protein in the CAT mouse. Curr. Eye Res. 12, 913–921.
Shiels A. and Bassnett S. 1996 Mutations in the founder of the MIP gene family underlie cataract development in the mouse. Nat. Genet. 12, 212–215.
Shiels A., Mackay D., Ionides A., Berry V., Moore A. and Bhattacharya S. 1998 A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant’ zonular pulverulent’ cataract, on chromosome 1q. Am. J. Hum. Genet. 62, 526–532.
Shiels A., Bennett T. M., Knopf H. L. S., Maraini G., Li A., Jiao X. and Hejtmancik J. F. 2008 The EPHA2 gene is associated with cataracts linked to chromosome 1p. Mol. Vis. 14, 2042–2055.
Shimada N., Aya-Murata T., Reza H.M. and Yasuda K. 2003 Cooperative action between L-Maf and Sox2 on δ-crystallin gene expression during chick lens development. Mech. Dev. 120, 455–465.
Sinha D., Wyatt M. K., Sarra R., Jaworski C., Slingsby C., Thaung C., Pannell L. et al. 2001 A temperature-sensitive mutation of Crygs in the murine Opj cataract. J. Biol. Chem. 276, 9308–9315.
Smidt M. P., Smits S. M., Bouwmeester H., Hamers F. P. T., van der Linden A. J. A., Hellemons A. J. C. G. M., et al. 2004 Early developmental failure of substantia nigra dopamine neurons in mice lacking the homeodomain gene Pitx3. Development 131, 1145–1155.
Smith R. S., Johnson K. R., Hawes N. L., Harris B. S., Sundberg J. P. and Davisson M. T. 1999 Lens epithelial proliferation cataract in segmental trisomy involving mouse chromosomes 4 and 17. Mamm. Genome 10, 102–106.
Spemann H. 1924 Über Organisatoren in der tierischen Entwicklung. Naturwissenschaften 48, 1092–1094.
Steele E. C., Kerscher S., Lyon M. F., Glenister P. H., Favor J., Wang J. H. and Church R. L. 1997 Identification of a mutation in the MP19 gene, Lim2, in the cataractous mouse mutant To3. Mol. Vis. 3, 5.
Steele Jr E. C., Lyon M. F., Favor J., Guillot P. V., Boyd Y. and Church R. L. 1998 A mutation in the connexin 50 (Cx50) gene is a candidate for the No2 mouse cataract. Curr. Eye Res. 17, 883–889.
Stout C., Goddenough D. A. and Paul D. L. 2004 Connexins: functions without junctions. Curr. Opin. Cell Biol. 16, 507–512. Takahasi K. R., Sakuraba Y. and Gondo Y. 2007 Mutational pattern and frequency of induced nucleotide changes in mouse ENU mutagenesis. BMC Mol. Biol. 8, 52; (doi: 10.1186/1471-2199-8-52).
Thaung C., West K., Clark B. J., McKie L., Morgan J. E., Arnold K. et al. 2002 Novel ENU-induced eye mutations in the mouse: models for human eye disease. Hum. Mol. Genet. 11, 755–767.
Tsonis P. A. and Fuentes E. J. 2006 Focus on molecules: Pax-6, the eye master. Exp. Eye Res. 83, 233–234.
van Agtmael T., Schlötzer-Schrehardt U., McKie L., Brownstein D. G., Lee A. W., Cross S. H. et al. 2005 Dominant mutations of Col4a1 result in basement membrane defects which lead to anterior segment dysgenesis and glomerulopathy. Hum. Mol. Genet. 14, 3161–3168.
Varnum D. S. and Stevens L. C. 1968 Aphakia, a new mutation in the mouse. J. Hered. 59, 147–150.
Vrensen G. F. J. M., Graw J. and de Wolf A. 1991 Nuclear breakdown during terminal differentiation of primary lens fibres in mice: a transmission electron microscopic study. Exp. Eye Res. 52, 647–659.
West S. K. 2000 Looking forward to 20/20: a focus on the epidemiology of eye diseases. Epidemiol. Rev. 22, 64–70.
White T. W. 2002 Unique and redundant connexin contributions to lens development. Science 295, 319–320.
White T.W., Goodenough D. A. and Paul D. L. 1998 Targeted ablation of connexin50 in mice results in microphthalmia and zonular pulverulent cataracts. J. Cell Biol. 143, 815–825.
White T. W., Sellito C., Paul D. L. and Goodenough D. A. 2001 Prenatal lens development in connexin43 and connexin50 double knockout mice. Invest. Ophthalmol. Vis. Sci. 42, 2916–2923.
Wistow G., Wyatt K., David L., Gao C., Bateman O., Bernstein S. et al. 2005 N-crystallin and the evolution of the βγ-crystallin superfamily in vertebrates. FEBS J. 272, 2276–2291.
Wolf N., Pendergrass W., Singh N., Swisshelm K. and Schwartz J. 2008 Radiation cataracts: mechanisms involved in their long delayed occurrence but then rapid progression. Mol. Vis. 14, 274–285.
Worgul B. V., Smilenov L., Brenner D. J., Junk A., Zhou W. and Hall E. J. 2002 Atm heterozygous mice are more sensitive to radiation-induced cataracts than their wild-type counterparts. Proc. Natl. Acad. Sci. USA 99, 9836–9839.
Xia C., Liu H., Chang B., Cheng C., Cheung D., Wang M. et al. 2006 Arginine 54 and tyrosine 118 residues of αA-crystallin are crucial for lens formation and transparency. Invest. Ophthalmol. Vis. Sci. 47, 3004–3010.
Yancey S. B., Biswal S. and Revel J.-P. 1992 Spatial and temporal patternms of distribution of the gap junction protein connexin43 during mouse gastrulation and organogenesis. Development 114, 203–212.
Yang Y.-G., Frappart P.-O., Frappart L., Wang Z.-Q. and Tong W.-M. 2006 A novel function of DNA repair molecule Nbs1 in terminal differentiation of the lens fibre cells and cataractogenesis. DNA Repair 5, 885–893.
Zhang T., Hua R., Xiao W., Burdon K. P., Bhattacharya S. S., Craig J. E. et al. 2009 Mutations of the EPHA2 receptor tyrosine kinase gene cause autosomal dominant congenital cataract. Hum. Mutat. Mutation in Brief 30, E603–E611.
Zhou L., Chen T. and Church R. L. 2002 Temporal expression of three mouse lens fibre cell membrane protein genes during early development. Mol. Vis. 8, 143–148.
Zwaan J. and Williams R. M. 1969 Cataracts and abnormal proliferation of the lens epithelium in mice carrying the CatFr gene. Exp. Eye Res. 8, 161–167.
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An erratum to this article can be found at http://dx.doi.org/10.1007/s12041-010-0004-3