Thrombin-deficient mutant of medaka, a model fish, displays serious retardation in blood coagulation.
Thrombin-deficient mutant of medaka, a model fish, displays serious retardation in blood coagulation.
复制标题
模型鱼青鳉的凝血酶缺陷突变体表现出严重的凝血迟缓。
DOI：
10.1093/bbb/zbaa098
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Hitomi K.
中科院分区：
文献类型：
--
作者：
Watanabe Y.;Oguri R.;Suzuki R.;Ishikawa Y.;Tatsukawa H.;Hashimoto H.;Hitomi K.
在血液凝固级联的最后阶段，凝血酶在纤维蛋白原的聚合加工中以及在因子XIII的额外活化中发挥中心作用，以稳定交联纤维蛋白。此外，凝血酶通过加工或与各种功能蛋白质相互作用而发挥可能的多种作用。正在进行几项研究，以阐明其他生理意义。为了进一步阐明凝血酶的意义并建立相关疾病模型，我们对研究模式鱼青鳉（Oryzias latipes）的直系同源基因进行了表征。用免疫技术分析了青鳉凝血酶原的组织分布。此外，凝血酶缺陷青鳉突变体是可行的建立利用基因组编辑方法。已建立的基因缺陷突变体表现出延迟凝血，即使在杂合子鱼。利用其易于处理的优势，这种特定的模型是有用的，在人类凝血疾病的医学研究领域的进一步调查。
At the last stage of the blood coagulation cascade, thrombin plays a central role in the processing of fibrinogen for the polymerization and in the additional activation of Factor XIII for the stable cross-linking of fibrin. In addition, thrombin carries out possible multiple roles via processing or interaction with various functional proteins. Several studies conducted in order to elucidate additional physiological significance are ongoing. To clarify further significance of thrombin and to establish an associated disease model, we characterized the orthologue gene for medaka (Oryzias latipes), a research model fish. Tissue distribution of medaka prothrombin has been immunotechnically analyzed. Furthermore, thrombin-deficient medaka mutants were viably established by utilizing a genome-editing method. The established gene-deficient mutants exhibited retarded blood coagulation even in the heterozygous fish. Taking advantage of their ease of handling, this specific model is useful for further investigation in medical research areas on human coagulation diseases.