E3 ubiquitin ligase RNF123-deficient mice exhibit reduced parasitemia and mortality in rodent malaria (Plasmodium yoelii 17XL) infection.

Abstract

Increased levels of several human ubiquitin ligases, including ring finger protein 123 (RNF123), in red blood cells with Plasmodium falciparum infection, have been reported. RNF123 is an E3 ubiquitin ligase that is highly expressed in erythroid cells. However, the function of the RNF123 gene and the relationship between the RNF123 gene and malarial parasite has not been clarified in vivo. In this study, we generated RNF123-deficient mice using the CRISPR/Cas9 system, and analyzed malaria susceptibility and erythrocyte morphology. The levels of parasitemia 5days post-infection and mortality 21days post-infection with the lethal type of rodent malaria (Plasmodium yoelii 17XL) in RNF123-deficient mice was significantly lower than that in wild-type mice. In contrast, red blood cell morphology in RNF123-deficient mice was almost normal. These results suggest that erythrocytic RNF123 plays a role in susceptibility to rodent malaria infection, but does not play a role in erythrocyte morphology.