Abstract:

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:TPI1^E105D-eGFP)] with the human TPI1^E105D (hTPI1^E105D) mutation, which is the most recurrent mutation in TPI DF patients. Overexpression of hTPI1^E105D 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.

Key words: triosephosphate isomerase deficiency (TPI DF), TPI1^E105D, zebrafish, disease model