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.

Comparative Analysis of Host Metabolic Alterations in Murine Malaria Models with Uncomplicated or Severe Malaria

“…To summarize, human malaria varies in its etiology with complications ranging from uncomplicated to severe malaria . Animal models for human disease serve as a valuable resource for the investigation of the disease etiology as well as for preclinical investigations. ,− However, a single animal infection model cannot mimic all symptoms of human malaria. ,, Since the spectrum of malaria in the different animal models imitates the diversity of human malaria, it has been advised to use the most appropriate model as per the research question asked. , Thereby, our comparison of uncomplicated malaria, hyperparasitemia, and cerebral malaria has been confounded by the use of different Plasmodium species and mouse strains. Nevertheless, our results highlight that both murine severe malaria models replicate similar metabolic signatures, with most of the metabolic intricacies being similar to what has been reported in human malaria. , Hemoglobin, lipid (fatty acids and steroids), amino acid, steroid hormone biosynthesis, caffeine, and nucleotide metabolism were found to be altered in all the murine malaria pathologies.…”

“…13,17−19 However, a single animal infection model cannot mimic all symptoms of human malaria. 13,17,19 Since the spectrum of malaria in the different animal models imitates the diversity of human malaria, it has been advised to use the most appropriate model as per the research question asked. 13,19 Thereby, our comparison of uncomplicated malaria, hyperparasitemia, and cerebral malaria has been confounded by the use of different Plasmodium species and mouse strains.…”

“…Thus, we have performed our experiments using murine models of Plasmodium infection. Murine models have proved to be useful for understanding specific host responses during Plasmodium infections and serve as valuable tools for preclinical research such as screening of drugs and vaccines. ,− Based on the mouse strain and the rodent malaria strains, different outcomes can be attained that would mimic the pathological symptoms of human malaria. ,− Thus, our objective was to use LC–MS-based serum metabolomics to detect metabolic perturbations that occur in the host during the different types of infection using murine models of malaria infection. − In our first set of studies, we performed a comparative analysis of mice groups suffering from nonlethal (P. yoelii 17XNL strain) and lethal (P.…”

A novel ENU-induced <i>Cpox</i> mutation causes microcytic hypochromic anemia in mice

“…Rodent malarial parasite infections were performed as described previously [10,11]. Red blood cells infected with the rodent malarial parasite, Plasmodium yoelii 17XL (P. yoelii 17XL), were stored as frozen stocks at −80 °C.…”