ATR localizes to the photoreceptor connecting cilium and deficiency leads to severe photoreceptor degeneration in mice

被引：25
作者：
Valdes-Sanchez, Lourdes [1 ]
De la Cerda, Berta [1 ]
Diaz-Corrales, Francisco J. [1 ]
Massalini, Simone [1 ]
Chakarova, Christina F. [2 ]
Wright, Alan F. [3 ]
Bhattacharya, Shomi S. [1 ,2 ]
机构：
[1] Andalusian Mol Biol & Regenerat Med Ctr CABIMER, Dept Cell Therapy & Regenerat Med, Seville 41092, Spain
[2] UCL Inst Ophthalmol, London EC1V 9EL, England
[3] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
来源：
HUMAN MOLECULAR GENETICS | 2013年 / 22卷 / 08期
关键词：
MICROTUBULE-ASSOCIATED PROTEINS; ATAXIA-TELANGIECTASIA; DNA-DAMAGE; MOUSE MODEL; SECKEL-SYNDROME; REGULATOR; RESPONSES; KINESIN; STRESS; RETINA;
D O I：
10.1093/hmg/dds563
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Ataxia-telangiectasia and Rad3 (ATR), a sensor of DNA damage, is associated with the regulation and control of cell division. ATR deficit is known to cause Seckel syndrome, characterized by severe proportionate short stature and microcephaly. We used a mouse model for Seckel disease to study the effect of ATR deficit on retinal development and function and we have found a new role for ATR, which is critical for the postnatal development of the photoreceptor (PR) layer in mouse retina. The structural and functional characterization of the ATR(/s) mouse retinas displayed a specific, severe and early degeneration of rod and cone cells resembling some characteristics of human retinal degenerations. A new localization of ATR in the cilia of PRs and the fact that mutant mice have shorter cilia suggests that the PR degeneration here described results from a ciliary defect.
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收藏
页码：1507 / 1515
页数：9
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