| First Author | Guo X | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 8005 | PubMed ID | 26272629 |
| Mgi Jnum | J:224989 | Mgi Id | MGI:5689941 |
| Doi | 10.1038/ncomms9005 | Citation | Guo X, et al. (2015) A short N-terminal domain of HDAC4 preserves photoreceptors and restores visual function in retinitis pigmentosa. Nat Commun 6:8005 |
| abstractText | 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. |
