BACKGROUND Ocular lens clouding is termed as cataract, which depending on the onset, is classified as congenital or age-related. Developing new cataract treatments requires new models. Thus far, Xenopus embryos have not been evaluated as a system for studying cataract. RESULTS We characterized the developmental process of lens formation in Xenopus laevis tailbuds and tadpoles, and we disrupted the orthologues of three mammalian cataract-linked genes in F0 by CRISPR/Cas9. We assessed the consequences of gene inactivation by combining external examination with histochemical analyses and functional vision assays. Inactivating the key metazoan eye development transcription factor gene pax6 produces a strong eye phenotype including an absence of eye tissue. Inactivating the genes for gap-junction protein and a nuclease, gja8 and dnase2b, produces lens defects that share several features of human cataracts, including impaired vision acuity, nuclei retention in lens fiber cells, and actin fibers disorganization. We tested the potential improvement of the visual acuity of gja8 crispant tadpoles upon treatment with the molecular chaperone 4-phenylbutyrate. CONCLUSION Xenopus is a valuable model organism to understand the molecular pathology of congenital eye defects, including cataracts, and to screen molecules with a potential to prevent or reverse cataracts.

中文翻译：

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模拟非洲爪蟾的晶状体疾病。

背景技术眼晶状体混浊被称为白内障，其根据发病被分类为先天性或年龄相关性。开发新的白内障治疗需要新的模型。迄今为止，非洲爪蟾胚胎尚未被评估为研究白内障的系统。结果我们表征了非洲爪蟾尾芽和蝌蚪晶状体形成的发育过程，并且我们通过 CRISPR/Cas9 破坏了 F0 中三个哺乳动物白内障相关基因的直向同源物。我们通过将外部检查与组织化学分析和功能视觉测定相结合来评估基因失活的后果。使关键的后生动物眼发育转录因子基因 pax6 失活会产生强烈的眼表型，包括缺乏眼组织。灭活间隙连接蛋白和核酸酶 gja8 和 dnase2b 的基因，产生的晶状体缺陷具有人类白内障的几个特征，包括视力受损、晶状体纤维细胞中的细胞核保留和肌动蛋白纤维紊乱。我们测试了 gja8 脆皮蝌蚪在用分子伴侣 4-苯基丁酸盐治疗后视力的潜在改善。结论 非洲爪蟾是了解先天性眼部缺陷（包括白内障）的分子病理学并筛选具有预防或逆转白内障潜力的分子的宝贵模型生物。