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在突变斑马鱼的原肾发育过程中 通过遗传补偿。

Genetic compensation by in pronephros development in mutant zebrafish.

机构信息

Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , People's Republic of China.

Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University , Mannheim , Germany.

出版信息

Cell Cycle. 2019 Oct;18(20):2683-2696. doi: 10.1080/15384101.2019.1656019. Epub 2019 Aug 26.

Abstract

Zebrafish erythropoietin a (epoa) is a well characterized regulator of red blood cell formation. Recent morpholino mediated knockdown data have also identified being essential for physiological pronephros development in zebrafish, which is driven by blocking apoptosis in developing kidneys. Yet, zebrafish mutants for have not been described so far. In order to compare a transient knockdown vs. permanent knockout for in zebrafish on pronephros development, we used CRISPR/Cas9 technology to generate knockout zebrafish mutants and we performed structural and functional studies on pronephros development. In contrast to morphants, zebrafish mutants showed normal pronephros structure; however, a previously uncharacterized gene in zebrafish, named , was identified and upregulated in mutants. knockdown altered pronephros development, which was further aggravated in mutants. Likewise, and morphants regulated similar and differential gene signatures related to kidney development in zebrafish. In conclusion, stable loss of during embryonic development can be compensated by leading to phenotypical discrepancies in knockdown and knockout zebrafish embryos.

摘要

斑马鱼促红细胞生成素 A(epoa)是一种经过充分研究的红细胞生成调节剂。最近的基于 morpholino 的敲低数据也表明, 在斑马鱼的生理前肾发育中是必不可少的,这是通过阻止发育中的肾脏细胞凋亡来驱动的。然而,到目前为止,还没有描述过 的斑马鱼突变体。为了比较瞬时敲低和永久性敲除 在斑马鱼前肾发育中的作用,我们使用 CRISPR/Cas9 技术生成了 敲除斑马鱼突变体,并对前肾发育进行了结构和功能研究。与 morphants 不同, 斑马鱼突变体显示出正常的前肾结构;然而,我们在 突变体中鉴定出了一个以前在斑马鱼中未被描述的基因,命名为 ,并上调了该基因的表达。 敲低改变了前肾发育,而在 突变体中进一步加重。同样, 和 morphants 调节了与斑马鱼肾脏发育相关的相似和不同的基因特征。总之,在胚胎发育过程中稳定缺失 可以通过 来补偿,导致 knockdown 和 knockout 斑马鱼胚胎在表型上存在差异。

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