Mouse NC/Jic strain provides novel insights into host genetic factors for malaria research

Abstract

Malaria is caused by Plasmodium parasites and is one of the most life-threatening infectious diseases in humans. Infection can result in severe complications such as cerebral malaria, acute lung injury/acute respiratory distress syndrome, and acute renal injury. These complications are mainly caused by P. falciparum infection and are major causes of death associated with malaria. There are a few species of rodent-infective malaria parasites, and mice infected with such parasites are now widely used for screening candidate drugs and vaccines and for studying host immune responses and pathogenesis associated with disease-related complications. We found that mice of the NC/Jic strain infected with rodent malarial parasites exhibit distinctive disease-related complications such as cerebral malaria and nephrotic syndrome, in addition to a rapid increase in parasitemia. Here, we focus on the analysis of host genetic factors that affect malarial pathogenesis and describe the characteristic features, utility, and future prospects for exploitation of the NC/Jic strain as a novel mouse model for malaria research.

Keywords: cerebral malaria; host susceptibility; malaria complications; mouse NC/Jic strain; rodent Plasmodium parasite.

Fig. 1.

(A) Brains of NC/Jic mice that were intravenously injected with Evans blue dye one hour before sacrifice. Breakdown of the blood-brain barrier results in a “bluish brain” and was observed NC/Jic with experimental CM after P. berghei ANKA infection (right side), but it was not observed in noninfected NC/Jic mice. (B) Histopathological analyses of P. berghei ANKA-infected NC/Jic mice (right side) and noninfected mice. Brain microvascular congestion was analyzed in infected mice after hematoxylin and eosin staining.

Fig. 2.

(A) Appearance of NC/Jic mice (littermates). Noninfected and nephrotic (indicated with an arrow) mice at 2 weeks after P. chabaudi chabaudi AS infection. (B) Kidneys of noninfected NC/Jic and nephrotic NC/Jic mice after P. chabaudi chabaudi AS infection. The kidneys of nephrotic mice shows yellowing (left side). (C) Plasma of noninfected NC/Jic and nephrotic NC/Jic mice after P. chabaudi chabaudi AS infection. Chylemia was observed in nephrotic NC/Jic mice (left side).