Phenotypic expression of pyruvate kinase deficiency and protection against malaria in a mouse model

摘要: The recombinant congenic mouse strains AcB55 and AcB61 are extremely resistant to malaria (Plasmodium chabaudi AS) despite the presence of susceptibility alleles at known Char1/Char2 resistance loci. Resistance in is controlled by a locus on chromosome 3 (Char4) shown be allelic with or tightly linked loss-of-function mutation pyruvate kinase (Pklr). show important splenomegaly prior infection caused expansion red pulp, display histological signs extramedullary erythropoiesis liver. Examination splenic cell populations flow cytometry demonstrates elevated numbers TER119-positive erythroid precursor cells (>30% total spleen cells), while RNA expression studies erythrocyte-specific transcripts such as globin, transferrin receptor, Nramp2/Slc11a2 both strains. Hematological profiling consistent anemia evidenced low erythrocyte counts, decreased hemoglobin, well abnormally high circulating reticulocytes (15–20%). These results strongly suggest that mutant Pklr allele (Pklr269A) AcB55/61 causes hemolytic compensated constitutive erythropoiesis, which turn protects mice against P. infection. possible molecular basis protective effect discussed under current investigation these two