UMMS Affiliation

Department of Ophthalmology

Date

7-2011

Document Type

Article

Subjects

Animals; Eye Proteins; Fluorescent Antibody Technique; Microphthalmos; Morpholinos; Mutation, Missense; Zebrafish; Zebrafish Proteins

Disciplines

Life Sciences | Medicine and Health Sciences | Ophthalmology

Abstract

Genetic mutations are frequently associated with diverse phenotypic consequences, which limits the interpretation of the consequence of a variation in patients. Mutations in the retinitis pigmentosa 2 (RP2) gene are associated with X-linked RP, which is a phenotypically heterogenic form of retinal degeneration. The purpose of this study was to assess the functional consequence of disease-associated mutations in the RP2 gene using an in vivo assay. Morpholino-mediated depletion of rp2 in zebrafish resulted in perturbations in photoreceptor development and microphthalmia (small eye). Ultrastructural and immunofluorescence analyses revealed defective photoreceptor outer segment development and lack of expression of photoreceptor-specific proteins. The retinopathy phenotype could be rescued by expressing the wild-type human RP2 protein. Notably, the tested RP2 mutants exhibited variable degrees of rescue of rod versus cone photoreceptor development as well as microphthalmia. Our results suggest that RP2 plays a key role in photoreceptor development and maintenance in zebrafish and that the clinical heterogeneity associated with RP2 mutations may, in part, result from its potentially distinct functional relevance in rod versus cone photoreceptors.

Comments

Citation: Patil SB, Hurd TW, Ghosh AK, Murga-Zamalloa CA, Khanna H (2011) Functional Analysis of Retinitis Pigmentosa 2 (RP2) Protein Reveals Variable Pathogenic Potential of Disease-Associated Missense Variants. PLoS ONE 6(6): e21379. doi:10.1371/journal.pone.0021379. Link to article on publisher's site

Copyright: © 2011 Patil et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Related Resources

Link to Article in PubMed

Journal Title

PloS one

PubMed ID

21738648

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