PUBLICATION

Functional Analysis of Retinitis Pigmentosa 2 (RP2) Protein Reveals Variable Pathogenic Potential of Disease-Associated Missense Variants

Authors
Patil, S.B., Hurd, T.W., Ghosh, A.K., Murga-Zamalloa, C.A., and Khanna, H.
ID
ZDB-PUB-110713-46
Date
2011
Source
PLoS One   6(6): e21379 (Journal)
Registered Authors
Khanna, Hemant
Keywords
none
MeSH Terms
  • Animals
  • Eye Proteins/genetics
  • Eye Proteins/metabolism*
  • Fluorescent Antibody Technique
  • Microphthalmos/genetics
  • Microphthalmos/metabolism
  • Morpholinos
  • Mutation, Missense/genetics
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
21738648 Full text @ PLoS One
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping