Development of a potent embryonic chick lens model for studying congenital cataracts in vivo.
Development of a potent embryonic chick lens model for studying congenital cataracts in vivo.
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DOI：
10.1038/s42003-021-01849-0
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发表时间：
2021-03-11
影响因子：
5.9
通讯作者：
Jiang JX
中科院分区：
文献类型：
--
作者：
Li Z;Gu S;Quan Y;Varadaraj K;Jiang JX
先天性白内障与基因突变有关，但其潜在机制仍不清楚。在这里，我们报道了一个胚胎鸡晶状体模型，该模型紧密再现了白内障的形成过程。我们采用了导致先天性白内障的显性阴性位点突变，连接蛋白、Cx50E48K、水通道蛋白0、AQP0R33C、α a -晶体蛋白、CRYAA R12C和R54C。在鸡胚发育早期，将含有这些突变体的重组逆转录病毒微注射到鸡晶状体的闭塞腔中。表达Cx50E48K可导致白内障，并伴有细胞核紊乱和细胞外间隙增大。aqporr33c的表达导致皮质性白内障，细胞外间隙增大，纤维细胞组织扭曲。αA晶体蛋白突变使晶状体光传输畸变，晶体蛋白聚集增加。总之，鸡胚晶状体中先天性突变基因的逆转录病毒表达与人类先天性白内障的特征非常相似。该模型将为研究白内障和其他遗传疾病的发生发展及其潜在机制提供一个有效、可靠的体内系统。Li等人报道了一个胚胎鸡晶状体模型来研究先天性白内障的发病。通过在鸡胚晶状体的腔内注射含有导致先天性白内障的突变体的重组逆转录病毒，他们发现他们的模型具有与人类先天性白内障非常相似的特征。
Congenital cataracts are associated with gene mutations, yet the underlying mechanism remains largely unknown. Here we reported an embryonic chick lens model that closely recapitulates the process of cataract formation. We adopted dominant-negative site mutations that cause congenital cataracts, connexin, Cx50E48K, aquaporin 0, AQP0R33C, αA-crystallin, CRYAA R12C and R54C. The recombinant retroviruses containing these mutants were microinjected into the occlusive lumen of chick lenses at early embryonic development. Cx50E48K expression developed cataracts associated with disorganized nuclei and enlarged extracellular spaces. Expression of AQP0R33C resulted in cortical cataracts, enlarged extracellular spaces and distorted fiber cell organization. αA crystallin mutations distorted lens light transmission and increased crystalline protein aggregation. Together, retroviral expression of congenital mutant genes in embryonic chick lenses closely mimics characteristics of human congenital cataracts. This model will provide an effective, reliable in vivo system to investigate the development and underlying mechanism of cataracts and other genetic diseases. Li et al. report an embryonic chick lens model to study the onset of congenital cataracts. By injecting recombinant retrovirus containing mutants that cause congenital cataract in lumen of embryonic chick lens, they show that their model exhibits cataract lens closely mimicking characteristics of human congenital cataracts.
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影响因子：
4
作者：
Banks EA;Toloue MM;Shi Q;Zhou ZJ;Liu J;Nicholson BJ;Jiang JX
通讯作者：
Jiang JX
影响因子：
4.2
作者：
Duman, Resat;Ertekin, Tolga;Guzel, Hilal
通讯作者：
Guzel, Hilal
影响因子：
1.4
作者：
HOCKWIN, O
通讯作者：
HOCKWIN, O
RCAS-RNAI：一种发育中的鸡视网膜的功能丧失方法。
影响因子：
--
作者：
Harpavat, S;Cepko, CL
通讯作者：
Cepko, CL
影响因子：
3.3
作者：
JIANG, JX;WHITE, TW;PAUL, DL
通讯作者：
PAUL, DL