A mutation in the start codon of γ-crystallin D leads to nuclear cataracts in the Dahl SS/Jr-Ctr strain.
A mutation in the start codon of γ-crystallin D leads to nuclear cataracts in the Dahl SS/Jr-Ctr strain.
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DOI：
10.1007/s00335-013-9447-1
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发表时间：
2013-04
期刊：
影响因子：
2.5
通讯作者：
Garrett, Michael R.
中科院分区：
文献类型：
--
作者：
Johnson, Ashley C.;Lee, Jonathan W.;Harmon, Ashlyn C.;Morris, Zaliya;Wang, Xuexiang;Fratkin, Jonathan;Rapp, John P.;Gomez-Sanchez, Elise;Garrett, Michael R.
白内障是失明的主要原因。白内障最常见的形式与年龄和紫外线有关，主要发生在老年人身上，而先天性白内障则出现在出生或幼儿时期。Dahl盐敏感（SS/Jr）大鼠是一种广泛使用的盐敏感性高血压模型，可伴有肾脏疾病。在20世纪80年代中期，达尔S群体中的一些动物出现了白内障，可能是自发突变的结果。将该突变固定并繁殖，建立了SS/Jr-Ctr亚株。SS/Jr-Ctr亚株被一名研究者专门用于研究类固醇和高血压的作用。采用经典的定位克隆方法，利用F1 (SS/Jr-Ctr X SHR) X SHR回交群体，将白内障基因定位在9号染色体上小于1 Mbp的高分辨率区域。1 Mbp区域仅包含13个基因，其中包括4个来自γ-晶体蛋白（Cryg）基因家族的基因，这些基因已知在白内障形成中起作用。对所有的γ-结晶蛋白进行测序，发现Crygd基因的起始密码子（ATG→GTG）出现一个新的点突变，导致SS/Jr-Ctr菌株眼睛中完全缺失Crygd蛋白。总之，在这种新型白内障模型中确定遗传原因可能为更好地了解白内障的发展提供机会，特别是在高血压的背景下。
Cataracts are a major cause of blindness. The most common forms of cataracts are age and UV related and develops mostly in the elderly, while congenital cataracts appear at birth or in early childhood. The Dahl salt-sensitive (SS/Jr) rat is an extensively used model of salt-sensitive hypertension that exhibits concomitant renal disease. In the mid 1980’s, cataracts appeared in a few animals in the Dahl S colony, presumably the result of a spontaneous mutation. The mutation was fixed and bred to establish the SS/Jr-Ctr substrain. The SS/Jr-Ctr substrain has been exclusively used by a single investigator to study the role of steroids and hypertension. Using a classical positional cloning approach, we localized the cataract gene with high-resolution to a less than 1 Mbp region on chromosome 9 using an F1 (SS/Jr-Ctr X SHR) X SHR backcross population. The 1 Mbp region contained only 13 genes, including 4 genes from the γ-crystallins (Cryg) gene family which are known to play a role in cataract formation. All of the γ-crystallins were sequenced and a novel point mutation in the start codon (ATG → GTG) of the Crygd gene was identified which led to the complete absence of CRYGD protein in the eyes of the SS/Jr-Ctr strain. In summary, the identification of the genetic cause in this novel cataract model may provide an opportunity to better understand the development of cataracts, particularly in the context of hypertension.
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DOI：
10.1097/01.asn.0000060572.13794.58
发表时间：
2003-05-01
影响因子：
13.6
作者：
Garrett, MR;Dene, H;Rapp, JP
通讯作者：
Rapp, JP
影响因子：
4.4
作者：
Chang, B;Hawes, NL;Roderick, TH
通讯作者：
Roderick, TH
影响因子：
13.6
作者：
Luebkemeier, Indra;Machura, Katharina;Kurtz, Armin
通讯作者：
Kurtz, Armin
影响因子：
3.5
作者：
Joe B;Saad Y;Dhindaw S;Lee NH;Frank BC;Achinike OH;Luu TV;Gopalakrishnan K;Toland EJ;Farms P;Yerga-Woolwine S;Manickavasagam E;Rapp JP;Garrett MR;Coe D;Apte SS;Rankinen T;Pérusse L;Ehret GB;Ganesh SK;Cooper RS;O'Connor A;Rice T;Weder AB;Chakravarti A;Rao DC;Bouchard C
通讯作者：
Bouchard C
影响因子：
2.5
作者：
Graw, J;Löster, J;de Angelis, MH
通讯作者：
de Angelis, MH