PUBLICATION
Systemic splicing factor deficiency causes tissue-specific defects: A zebrafish model for Retinitis pigmentosa
- Authors
- Linder, B., Dill, H., Hirmer, A., Brocher, J., Lee, G.P., Mathavan, S., Bolz, H.J., Winkler, C., Laggerbauer, B., and Fischer, U.
- ID
- ZDB-PUB-101108-35
- Date
- 2011
- Source
- Human molecular genetics 20(2): 368-377 (Journal)
- Registered Authors
- Brocher, Jan, Mathavan, S., Winkler, Christoph
- Keywords
- none
- Datasets
- GEO:GSE20424
- MeSH Terms
-
- Organ Specificity
- Phenotype
- Gene Knockdown Techniques
- Animals
- Disease Models, Animal*
- RNA Splicing/genetics
- Zebrafish*
- Haploinsufficiency/genetics
- Gene Expression Regulation, Developmental
- Photoreceptor Cells, Vertebrate/metabolism
- Photoreceptor Cells, Vertebrate/pathology
- Retinitis Pigmentosa/genetics
- Retinitis Pigmentosa/pathology*
- Eye Proteins/genetics*
- Eye Proteins/metabolism*
- Retina/metabolism
- Retina/physiopathology
- Mutation
- PubMed
- 21051334 Full text @ Hum. Mol. Genet.
Citation
Linder, B., Dill, H., Hirmer, A., Brocher, J., Lee, G.P., Mathavan, S., Bolz, H.J., Winkler, C., Laggerbauer, B., and Fischer, U. (2011) Systemic splicing factor deficiency causes tissue-specific defects: A zebrafish model for Retinitis pigmentosa. Human molecular genetics. 20(2):368-377.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping