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-g6pd M118-144 -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-g6pd M118-144 -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-g6pd M118-144 -egfp) zebrafish line. On the other hand, there is no morphological abnormality in the transgenic Tg(zgata1-g6pd M118-144 -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.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited enzymopathy in humans and is associated with a predisposition to hemolysis. However, there are few animal models to that adequately mimic associated human disease states that could be used to evaluate strategies to address clinical syndromes attributable to G6PD deficiency. In the present study, we aimed to establish a stable transgenic zebrafish model of G6PD deficiency that recapitulates the clinical manifestations of G6PD deficiency. We incorporated a stable transgene of G6PD lacking nucleotides from 1315 to 1443 denoted Tg(zgata1:g6pd M1315-1443 -egfp).Functional analysis showed that Tg(zgata1:g6pd M1315-1443 -egfp) transgenic zebrafish demonstrate a decrease in g6pd activity, reduced GSH levels and hemoglobin content, and increases in pericardial edema in response to α -naphthol exposure, similar to human subjects with G6PD deficiency. We detected no other significant phenotypic abnormalities compared to controls.Taken together, these observations indicate that the Tg(zgata1:g6pd M1315-1443 -egfp) zebrafish line mirrors key clinical manifestations of G6PD deficiency in humans. This model may facilitate mechanistic studies and promote translational research related to G6PD deficiency.