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bioRxiv · 10.1101/2020.04.28.066779

Establishment of a stable zg6pdM118-144 transgenic zebrafish model of glucose-6-phosphate dehydrogenase deficiency

Zhou, Y.-H.·Ren, P.-P.·Xia, H.-X.·Tuo, Y.-Y.·Song, J.·Shang, L.-J.·Jin, J.·He, Z.-X.·Shu, L.
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Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common genetic defect and enzymopathy with a wide distribution and increased public health concern, predisposes subjects succumb to oxidative stress. G6PD deficiency has been associated with hemolysis. Clinically, G6PD deficiency is asymptomatic and the clinical manifestations occur with the exposure to certain agents. Due to the lack of suitable animal models that can predict the clinical hemolytic potential of drugs, it needs an appropriate research model to fully recapitulate the manifestations of G6PD deficiency in clinic, to optimize the malaria therapy and promote anti-malarias development. The present study has displayed a stable transgenic Tg(zgata1-g6pdM118-144-egfp) zebrafish model with G6PD deficiency which mimics the clinical features of G6PD deficiency phenotypically and functionally. The findings showed that there was an inadequate level of reduced GSH in the transgenic Tg(zgata1-g6pdM118-144-egfp) zebrafish line in the presence or absence of α-naphthol, compared to the wildtype zebrafish, indicating an attenuation of g6pd activity in the transgenic zebrafish line. In addition, the observations show that there is a less abundance of g6pd in the transgenic Tg(zgata1-g6pdM118-144-egfp) zebrafish line. On the other hand, there is no morphological abnormality in the transgenic Tg(zgata1-g6pdM118-144-egfp) zebrafish line. Taken together, our work has delivered a novel stable transgenic zebrafish model of G6PD deficiency that will facilitate the mechanistic and functional elucidation for the role of G6PD in erythrocytic pathophysiology. This model will promote the translational research for the drug development, in particular, for anti-malarias development.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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Zhou, Y.-H., Ren, P.-P., Xia, H.-X., Tuo, Y.-Y., Song, J., Shang, L.-J., Jin, J., He, Z.-X., Shu, L.. 2020-04-30. Establishment of a stable zg6pdM118-144 transgenic zebrafish model of glucose-6-phosphate dehydrogenase deficiency. https://doi.org/10.1101/2020.04.28.066779

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