Biochemical characterization of medaka (Oryzias latipes) fibrinogen gamma and its gene disruption resulting in anemia as a model fish
Biochemical characterization of medaka (Oryzias latipes) fibrinogen gamma and its gene disruption resulting in anemia as a model fish
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DOI：
10.1093/jb/mvac065
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发表时间：
2022-08-23
影响因子：
2.7
通讯作者：
Hitomi，Kiyotaka
中科院分区：
文献类型：
--
作者：
Meng，Qi;Watanabe，Yuko;Hitomi，Kiyotaka
在血液凝固的最后阶段，纤维蛋白原被凝血酶加工成不溶性纤维蛋白，导致纤维样结构形成。通过血液转氨酶（因子XIII）的催化作用，通过纤维蛋白γ亚基之间的进一步交联反应，该分子获得进一步的物理稳定性。同时，由于纤维蛋白原在各种细胞和组织中表达，该分子除了在血液凝固中的作用之外还可以表现出其他功能。为了建立一个研究异常凝血机制的系统，并探讨其生理功能，我们以青鳉（Oryzias latipes）为模型鱼，构建了纤维蛋白原γ亚基蛋白基因缺陷突变体，并对其进行了组织分布和底物性质等生化分析。通过基因组编辑进行基因缺失，两种不同的突变体显示出凝血迟缓。突变体表现出较低的红细胞压积与异常的红细胞成熟，这表明纤维蛋白缺乏引起严重的贫血，也出现作为模型的纤维蛋白功能的调查。
At the final stages of blood coagulation, fibrinogen is processed into insoluble fibrin by thrombin resulting in fibril-like structure formation. Via further cross-linking reactions between the fibrin gamma subunit by the catalytic action of blood transglutaminase (Factor XIII), this molecule gains further physical stability. Meanwhile, since fibrinogen is expressed in various cells and tissues, this molecule can exhibit other functions apart from its role in blood coagulation. To create a system studying on aberrant coagulation and investigate the physiological functions, using a model fish medaka (Oryzias latipes), we established gene-deficient mutants of fibrinogen gamma subunit protein in parallel with its biochemical analysis, such as tissue distribution pattern and substrate properties. By genetic deletion via genome editing, two distinct mutants displayed retardation of blood coagulation. The mutants showed lower hematocrit with aberrant erythrocyte maturation, which indicates that fibrin deficiency caused severe anemia, and also appeared as a model for investigation of the fibrin function.