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A short N-terminal domain of HDAC4 preserves photoreceptors and restores visual function in retinitis pigmentosa
- Source :
- Nature communications
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Retinitis pigmentosa is a leading cause of inherited blindness, with no effective treatment currently available. Mutations primarily in genes expressed in rod photoreceptors lead to early rod death, followed by a slower phase of cone photoreceptor death. Rd1 mice provide an invaluable animal model to evaluate therapies for the disease. We previously reported that overexpression of histone deacetylase 4 (HDAC4) prolongs rod survival in rd1 mice. Here we report a key role of a short N-terminal domain of HDAC4 in photoreceptor protection. Expression of this domain suppresses multiple cell death pathways in photoreceptor degeneration, and preserves even more rd1 rods than the full-length HDAC4 protein. Expression of a short N-terminal domain of HDAC4 as a transgene in mice carrying the rd1 mutation also prolongs the survival of cone photoreceptors, and partially restores visual function. Our results may facilitate the design of a small protein therapy for some forms of retinitis pigmentosa.
- Subjects :
- Genotype
genetic structures
Transgene
General Physics and Astronomy
Mice, Transgenic
Biology
medicine.disease_cause
Histone Deacetylases
Article
General Biochemistry, Genetics and Molecular Biology
Mice
Retinitis pigmentosa
Electroretinography
medicine
Animals
Humans
Photoreceptor Cells
Vision, Ocular
Regulation of gene expression
Mutation
Multidisciplinary
Gene therapy of the human retina
medicine.diagnostic_test
HEK 293 cells
General Chemistry
medicine.disease
HDAC4
Molecular biology
eye diseases
Protein Structure, Tertiary
3. Good health
Cell biology
Repressor Proteins
HEK293 Cells
Gene Expression Regulation
sense organs
Gene Deletion
Retinitis Pigmentosa
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....d1c0b7c3a8b5b6ff82afba95496f74ad