变位子插入导致 ctnnb2 转录不稳定,导致母性效应斑马鱼 (ichabod) (ich) 突变
Zsombor Varga1, Ferenc Kagan1,2, Shingo Maegawa3
1Department of Genetics, ELTE Eötvös Loránd University, Budapest, Hungary.
bioRxiv : the preprint server for biology
|March 17, 2025
概括
斑马鱼中的伊卡博德突变通过破坏Wnt信号,导致腹腔胚胎. 研究人员确定了对转录稳定性降低和发育缺陷负责的ctnnb2基因中的转子插入.
科学领域:
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 母性效应突变可以通过影响基因表达来破坏胚胎发育.
- 斑马鱼中的Ichabod (ich) 突变导致腹部胚胎,与Wnt信号通路缺陷有关.
- 以前的研究表明ctnnb2转录水平降低,但没有确定致病突变.
研究的目的:
- 为了确定斑马鱼中 ichabod (ich) 突变的分子基础.
- 调查转子子活性在斑马鱼发育和基因调节中的作用.
- 了解早期胚胎发生过程中母体转录稳定性的调节.
主要方法:
- 长读序列测定用于识别对其表型负责的基因突变.
- 报告员测试评估突变对ctnnb2mRNA稳定性的影响.
- 在斑马鱼中对CMC增强器/抑制器-突变器 (CMC-EnSpm) 转位子的全基因组映射.
主要成果:
- 这种ich表型是由CMC-Enhancer/Suppressor-mutator (CMC-EnSpm) 转位子插入ctnnb2基因的3'UTR引起的.
- 这种转子体插入在早期发育过程中显著降低了ctnnb2mRNA的稳定性.
- 在多个斑马鱼菌株中检测到CMC-EnSpm元素的持续转移活性.
结论:
- 基因突变的分子基础是内源转子体插入,影响母亲的转录稳定性.
- 内源转位子具有持续的突变性潜力,可以影响胚胎发育.
- 这项研究揭示了对母体转录调节和斑马鱼基因组的动态性质的新见解.
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