期刊
HUMAN MOLECULAR GENETICS
卷 25, 期 10, 页码 2005-2012出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddw075
关键词
-
资金
- National Institutes of Health (NIH) [EY022372, EY08123, EY019298, EY014800-039003]
- Foundation Fighting Blindness
- University of Massachusetts Center for Clinical and Translational Sciences (UMCCTS)
- Massachusetts Lions Eye Research Funds
- RPB Nelson Trust Award
- Retina Research Foundation (Alice McPherson, MD), Houston
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 Rpgr(ko/Y) mice with a heterozygous hypomorphic allele of Cep290 (Cep290(rd16/+)) but not of a heterozygous null allele of Cep290 (Cep290(null/+)) 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 similar to 7 months of age in the Rpgr(ko/Y) mice. We also observed disorganized photoreceptor outer-segment morphology and defective trafficking of opsins in the Rpgr(ko/Y)::Cep290(rd16/+) 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据