在小鼠和人类中的Ovol2促进子突变揭示了物种特异的表型分歧
Sweetu Susan Sunny1, Jitka Lachova1, Petr Kasparek2
1Laboratory of Transcriptional Regulation, Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20, Prague 4, Prague, Czech Republic.
Human molecular genetics
|November 16, 2023
概括
在OVOL2促销器的致病变体导致后方多形角膜变 (PPCD) 1. 鼠标模型显示,Ovol2促进子突变增加了Ovol2的表达,但不能完全复制PPCD1,这表明了物种特异性差异.
科学领域:
- 遗传学 是一个遗传学.
- 眼科医生 眼科 眼科
- 发展生物学 发展生物学
背景情况:
- 在OVOL2促销器的致病变体导致后方多形角膜变 (PPCD) 1通过异卵巢OVOL2mRNA表达.
- 在不同物种中,OVOL2促进体的保护性很高.
研究的目的:
- 在小鼠模型中生成和分析Ovol2促进子突变的等位列序列.
- 研究Ovol2促进体变异对Ovol2表达和眼睛表现型的功能后果.
主要方法:
- 在小鼠中产生异构卵子2促进子突变,包括人类PPCD1-相关的c.-307T>C变异.
- 在角膜内皮中评估Ovol2mRNA水平.
- 在成年和胚胎小鼠中评估了眼睛表型.
主要成果:
- 该c.-307T>C突变增加了角膜内皮中的Ovol2表达.
- 在成年c.-307T>C突变小鼠的一小部分中观察到眼睛表型,如虹膜-角膜粘附和角膜不透明,在胚胎阶段透率更高.
- 包含Ovol2结合部位的删除 (c.-307_-320del) 也提高了Ovol2的调节,并导致了类似的表型.
- 尽管Ovol2表达增加了,但在小鼠中没有观察到典型的内皮缩症.
结论:
- 卵子2促销器变体可以在小鼠中引起主要的眼睛表型,这表明它在眼睛发育中的作用.
- 在小鼠中缺乏类似PPCD1的内皮质变质表明角膜内皮细胞生物学中存在特定物种的差异.
- OVOL2基因及其促进体是理解和治疗某些角膜缩症的潜在目标.
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