| First Author | Rao KN | Year | 2016 |
| Journal | Hum Mol Genet | Volume | 25 |
| Issue | 10 | Pages | 2005-2012 |
| PubMed ID | 26936822 | Mgi Jnum | J:235807 |
| Mgi Id | MGI:5803743 | Doi | 10.1093/hmg/ddw075 |
| Citation | Rao KN, et al. (2016) Ciliopathy-associated protein CEP290 modifies the severity of retinal degeneration due to loss of RPGR. Hum Mol Genet 25(10):2005-2012 |
| abstractText | Mutations in RPGR (retinitis pigmentosa GTPase regulator) are the most common cause of X-linked RP, a severe blindness disorder. RPGR mutations result in clinically variable disease with early- to late-onset phenotypic presentation. Molecular mechanisms underlying such heterogeneity are unclear. Here we show that phenotypic expression of Rpgr-loss in mice is influenced genetically by the loss of Cep290, a human ciliopathy gene. We found that Rpgrko/Y mice with a heterozygous hypomorphic allele of Cep290 (Cep290rd16/+) but not of a heterozygous null allele of Cep290 (Cep290null/+) or of other ciliopathy genes, Rpgrip1, Nphp1, Nphp4 and Nphp5, exhibit relatively early onset (by 3 months of age) retinal degeneration and dysfunction when compared with the onset at approximately 7 months of age in the Rpgrko/Y mice. We also observed disorganized photoreceptor outer-segment morphology and defective trafficking of opsins in the Rpgrko/Y::Cep290rd16/+ mice. Together with a physical interaction between RPGR and the C-terminal domain of CEP290, our data suggest that RPGR and CEP290 genetically interact and highlight the involvement of hypomorphic alleles of genes as potential modifiers of heterogeneous retinal ciliopathies. |
