Journal Article

Systemic splicing factor deficiency causes tissue-specific defects: a zebrafish model for retinitis pigmentosa<sup>†</sup>

Bastian Linder, Holger Dill, Anja Hirmer, Jan Brocher, Gek Ping Lee, Sinnakaruppan Mathavan, Hanno Jörn Bolz, Christoph Winkler, Bernhard Laggerbauer and Utz Fischer

in Human Molecular Genetics

Volume 20, issue 2, pages 368-377
Published in print January 2011 | ISSN: 0964-6906
Published online November 2010 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddq473
Systemic splicing factor deficiency causes tissue-specific defects: a zebrafish model for retinitis pigmentosa†

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Retinitis pigmentosa (RP) is a common hereditary eye disease that causes blindness due to a progressive loss of photoreceptors in the retina. RP can be elicited by mutations that affect the tri-snRNP subunit of the pre-mRNA splicing machinery, but how defects in this essential macromolecular complex transform into a photoreceptor-specific phenotype is unknown. We have modeled the disease in zebrafish by silencing the RP-associated splicing factor Prpf31 and observed detrimental effects on visual function and photoreceptor morphology. Despite reducing the level of a constitutive splicing factor, no general defects in gene expression were found. Instead, retinal genes were selectively affected, providing the first in vivo link between mutations in splicing factors and the RP phenotype. Silencing of Prpf4, a splicing factor hitherto unrelated to RP, evoked the same defects in vision, photoreceptor morphology and retinal gene expression. Hence, various routes affecting the tri-snRNP can elicit tissue-specific gene expression defects and lead to the RP phenotype.

Journal Article.  5701 words.  Illustrated.

Subjects: Genetics and Genomics

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