Triosephosphate isomerase deficiency (TPI DF) is a severe multisystem degenerative disease, manifested clinically as hemolytic anemia, neuromuscular abnormalities, and susceptibility to infection, frequently leading to death within 5 years of onset. There is a lack of effective clinical treatment as the pathogenesis underlying TPI DF remains largely unknown. In this study, we generate a transgenic zebrafish line [Tg(Ubi:TPI1E105D-eGFP)] with the human TPI1E105D (hTPI1E105D) mutation, which is the most recurrent mutation in TPI DF patients. Overexpression of hTPI1E105D affects the development of erythroid and myeloid cells and leads to impaired neural and muscular development. In conclusion, we create a TPI DF zebrafish model to recapitulate the majority clinical features of TPI DF patients, providing a new animal model for pathogenesis study and drug screening of TPI DF.
磷酸丙糖异构酶缺乏症(triosephosphate isomerase deficiency，TPI DF)是一种严重的多系统退行性疾病，通常表现为溶血性贫血、神经肌肉功能障碍和易感染，患者多于起病5年内死亡。目前尚不清楚TPI DF的具体发病机制，缺乏有效的临床治疗方法。本研究选取TPI DF患者中最常见的突变位点TPI1E105D，构建了表达人源性TPI1E105D(hTPI1E105D)的转基因斑马鱼(Danio rerio)模型[Tg(Ubi:TPI1E105D-eGFP)]。功能分析表明，过表达TPI1E105D影响红系及髓系细胞发育、导致神经以及肌肉发育异常。综上所述，本研究构建了磷酸丙糖异构酶缺乏症的斑马鱼疾病模型，并能够复现TPI DF患者的大部分临床表型，该模型为后续研究TPI DF的发病机制及药物筛选提供了新的实验动物模型。.
Keywords: TPI1E105D; disease model; triosephosphate isomerase deficiency (TPI DF); zebrafish.