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Mutations in the human\n                    <jats:italic>CRX<\/jats:italic>\n                    gene are associated with dominant inherited retinopathies Retinitis Pigmentosa (RP), Cone\u2010Rod Dystrophy (CoRD), and Leber Congenital Amaurosis (LCA), of varying severity. In vitro and in vivo assessment of mutant CRX proteins have revealed pathogenic mechanisms for several mutations, but no comprehensive mutation\u2010disease correlation has yet been reported.\n                    <jats:styled-content>Results:<\/jats:styled-content>\n                    Here we describe four different classes of disease\u2010causing\n                    <jats:italic>CRX<\/jats:italic>\n                    mutations, characterized by mutation type, pathogenetic mechanism, and the molecular activity of the mutant protein: (1) hypomorphic missense mutations with reduced DNA binding, (2) antimorphic missense mutations with variable DNA binding, (3) antimorphic frameshift\/nonsense mutations with intact DNA binding, and (4) antimorphic frameshift mutations with reduced DNA binding. Mammalian models representing three of these classes have been characterized.\n                    <jats:styled-content>Conclusions:<\/jats:styled-content>\n                    Models carrying Class I mutations display a mild dominant retinal phenotype and recessive LCA, while models carrying Class III and IV mutations display characteristically distinct dominant LCA phenotypes. These animal models also reveal unexpected pathogenic mechanisms underlying\n                    <jats:italic>CRX<\/jats:italic>\n                    \u2010associated retinopathies. The complexity of genotype\u2010phenotype correlation for\n                    <jats:italic>CRX<\/jats:italic>\n                    \u2010associated diseases highlights the value of developing comprehensive \u201ctrue\u2010to\u2010disease\u201d animal models for understanding pathologic mechanisms and testing novel therapeutic approaches.\n                    <jats:italic>Developmental Dynamics 243:1153\u20131166, 2014<\/jats:italic>\n                    . \u00a9 2014 Wiley Periodicals, Inc.\n                  <\/jats:p>","DOI":"10.1002\/dvdy.24151","type":"journal-article","created":{"date-parts":[[2014,6,3]],"date-time":"2014-06-03T05:29:46Z","timestamp":1401773386000},"page":"1153-1166","source":"Crossref","is-referenced-by-count":52,"title":["Mechanisms of blindness: Animal models provide insight into distinct\n                    <i>CRX<\/i>\n                    \u2010associated retinopathies"],"prefix":"10.1002","volume":"243","author":[{"given":"Nicholas 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