Department of Animal & Avian Sciences and Department of Cell Biology & Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Department of Animal & Avian Sciences and Department of Cell Biology & Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Mol Genet Metab. 2019 Nov;128(3):204-212. doi: 10.1016/j.ymgme.2018.12.007. Epub 2018 Dec 24.
Coordination of iron acquisition and heme synthesis is required for effective erythropoiesis. The small teleost zebrafish (Danio rerio) is an ideal vertebrate animal model to replicate various aspects of human physiology and provides an efficient and cost-effective way to model human pathophysiology. Importantly, zebrafish erythropoiesis largely resembles mammalian erythropoiesis. Gene discovery by large-scale forward mutagenesis screening has identified key components in heme and iron metabolism. Reverse genetic screens, using morpholino-knockdown and CRISPR/Cas9, coupled with the genetic tractability of the developing embryo have further accelerated functional studies. Ultimately, the ex utero development of zebrafish embryos combined with their transparency and developmental plasticity could provide a deeper understanding of the role of iron and heme metabolism during early vertebrate embryonic development.
铁的获取和血红素合成的协调是有效红细胞生成所必需的。小型硬骨鱼斑马鱼（Danio rerio）是一种理想的脊椎动物模型，可以复制人类生理学的各个方面，并提供一种高效且具有成本效益的方法来模拟人类病理生理学。重要的是，斑马鱼的红细胞生成在很大程度上类似于哺乳动物的红细胞生成。通过大规模正向诱变筛选发现的基因，确定了血红素和铁代谢中的关键成分。利用反义寡核苷酸敲低和 CRISPR/Cas9 的反向遗传筛选，再加上发育中胚胎的遗传可操作性，进一步加速了功能研究。最终，斑马鱼胚胎的体外发育，加上其透明性和发育可塑性，可以更深入地了解铁和血红素代谢在早期脊椎动物胚胎发育中的作用。
