Journal Article

CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina

Adrienne K. Mehalow, Shuhei Kameya, Richard S. Smith, Norman L. Hawes, James M. Denegre, James A. Young, Lesley Bechtold, Neena B. Haider, Ulrich Tepass, John R. Heckenlively, Bo Chang, Jürgen K. Naggert and Patsy M. Nishina

in Human Molecular Genetics

Volume 12, issue 17, pages 2179-2189
Published in print September 2003 | ISSN: 0964-6906
Published online September 2003 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddg232
CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina

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Mutations within the CRB1 gene have been shown to cause human retinal diseases including retinitis pigmentosa and Leber congenital amaurosis. We have recently identified a mouse model, retinal degeneration 8 (rd8) with a single base deletion in the Crb1 gene. This mutation is predicted to cause a frame shift and premature stop codon which truncates the transmembrane and cytoplasmic domain of CRB1. Like in Drosophila crumbs (crb) mutants, staining for adherens junction proteins known to localize to the external limiting membrane, the equivalent of the zonula adherens in the mammalian retina, is discontinuous and fragmented. Shortened photoreceptor inner and outer segments are observed as early as 2 weeks after birth, suggesting a developmental defect in these structures rather than a degenerative process. Photoreceptor degeneration is observed only within regions of retinal spotting, which is seen predominantly in the inferior nasal quadrant of the eye, and is caused by retinal folds and pseudorosettes. Photoreceptor dysplasia and degeneration in Crb1 mutants strongly vary with genetic background, suggesting that the variability in phenotypes of human patients that carry mutations in CRB1 may be due to interactions with background modifiers in addition to allelic variations. The Crb1rd8 mouse model will facilitate the analysis of Crb1 function in the neural retina and the identification of interacting factors as candidate retinal disease genes.

Journal Article.  6745 words.  Illustrated.

Subjects: Genetics and Genomics

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