A splicing mutation in aryl hydrocarbon receptor associated with retinitis pigmentosa

doi:10.1093/hmg/ddy165

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	A splicing mutation in aryl hydrocarbon receptor associated with retinitis pigmentosa
	Zhou, Yu 4,6; Li, Shujin 5,6; Huang, Lulin 4,6; Yang, Yeming 4,6; Zhang, Lin 4,6; Yang, Mu 5; Liu, Wenjing 6; Ramasamy, Kim 2; Jiang, Zhilin 4,6; Sundaresan, Periasamy 1
刊名	HUMAN MOLECULAR GENETICS
	2018
卷号	27 期号:14 页码:2563-2572
ISSN号	0964-6906
DOI	10.1093/hmg/ddy165
产权排序	2
文献子类	Article
英文摘要	Retinitis pigmentosa (RP) refers to a group of retinal degenerative diseases, which often lead to vision loss. Although 70 genes have been identified in RP patients, the genetic cause of approximately 30% of RP cases remains unknown. We aimed to identify the cause of the disease in a cohort of RP families by whole exome sequencing. A rare homozygous splicing variant, c.1160+1G> A, which introduced skipping of exon 9 of the aryl hydrocarbon receptor (AHR), was identified in family RD-134. This variant is very rare in several exome databases and leads to skipping of exon 9 in the transcript. AHR is expressed in the human retina and is a ligand-activated transcription factor with multiple functions. Mutant AHR failed to promote 2, 3, 7, 8-tetra-chlorodibenzo-p-dioxin (TCDD)-induced xenobiotic responsive element (XRE) luciferase activity. In parallel, mutation in AHR abolished activation of its downstream target gene, such as CYP1A1 and CYP1A2. To investigate the in vivo roles of Ahr in the retina, we generated a retina-specific conditional knockout mouse model of Ahr. Comparing with wild-type mouse, Ahr knockout mice exhibited reduced electroretinogram responses at 9 months of age. Retinal histology revealed retinal histology showed the degeneration of photoreceptors with a thinner outer nuclear layer. Thus, our data demonstrate that AHR is associated with RP.
学科主题	Molecular Biology ; Genetics
URL标识	查看原文
WOS关键词	INHERITED RETINAL DYSTROPHIES ; AH-RECEPTOR ; LIGAND-BINDING ; GENE ; PREVALENCE ; IDENTIFICATION ; DEGENERATION ; MICE ; CRB1 ; POLYMORPHISM
WOS研究方向	Biochemistry & Molecular Biology ; Genetics & Heredity
语种	英语
出版者	OXFORD UNIV PRESS
WOS记录号	WOS:000438579900012
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/30680]
专题	国家天然药物工程技术研究中心_天然产物研究
作者单位	1.Aravind Eye Hosp, Dept Genet, Aravind Med Res Fdn, Madurai, Tamil Nadu, India 2.Aravind Eye Hosp, Retina Vitreous Serv, Madurai, Tamil Nadu, India; 3.Sichuan Acad Med Sci, Inst Lab Anim Sci, Chengdu 610072, Sichuan, Peoples R China; 4.Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, Sichuan 610072, China; 5.Chinese Acad Sci, Chengdu Inst Biol, Sichuan Translat Med Res Hosp, Chengdu 610072, Sichuan, Peoples R China; 6.Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Sichuan Prov Key Lab Human Dis Gene Study, Chengdu 610072, Sichuan, Peoples R China;
推荐引用方式 GB/T 7714	Zhou, Yu,Li, Shujin,Huang, Lulin,et al. A splicing mutation in aryl hydrocarbon receptor associated with retinitis pigmentosa[J]. HUMAN MOLECULAR GENETICS,2018,27(14):2563-2572.
APA	Zhou, Yu.,Li, Shujin.,Huang, Lulin.,Yang, Yeming.,Zhang, Lin.,...&Yang, Zhenglin.(2018).A splicing mutation in aryl hydrocarbon receptor associated with retinitis pigmentosa.HUMAN MOLECULAR GENETICS,27(14),2563-2572.
MLA	Zhou, Yu,et al."A splicing mutation in aryl hydrocarbon receptor associated with retinitis pigmentosa".HUMAN MOLECULAR GENETICS 27.14(2018):2563-2572.