| First Author | Min-Oo G | Year | 2007 |
| Journal | Blood Cells Mol Dis | Volume | 39 |
| Issue | 1 | Pages | 63-9 |
| PubMed ID | 17466543 | Mgi Jnum | J:141722 |
| Mgi Id | MGI:3819314 | Doi | 10.1016/j.bcmd.2007.03.003 |
| Citation | Min-Oo G, et al. (2007) Pyruvate kinase deficiency: correlation between enzyme activity, extent of hemolytic anemia and protection against malaria in independent mouse mutants. Blood Cells Mol Dis 39(1):63-9 |
| abstractText | AcB55, AcB61 and CBA/N-Pk(slc) mice carry loss of function mutations in the erythrocyte specific pyruvate kinase gene (Pklr). In AcB55 and AcB61 (Pklr(I90N)) PK deficiency is protective against blood-stage malaria. The mechanistic basis of protection against malaria is unknown and was studied in these two mutant alleles in vivo. The Pklr(G338D) mutation of the CBA/N-Pk(slc) mutant is shown to be more deleterious than the Pklr(I90N) allele with respect to enzymatic activity and severity of hemolytic anemia, with a more dramatic reduction in the half-life of erythrocytes (increased turnover) in the CBA/N-Pk(slc) mice. The CBA/N-Pk(slc) mice are also shown to be highly resistant to infection with Plasmodium chabaudi AS when compared to CBA/J and CBA/N controls. Resistance to malaria, measured as lower levels of blood-stage replication of P. chabaudi, rapid elimination of infected erythrocytes and increased survival to infection, was greater in the Pklr(G338D) mutant, CBA/N-Pk(slc), than in the Pklr(I90N) mutant strains, AcB55/AcB61. These results strongly suggest a correlation between severity of PK-deficiency and extent of protection against malaria. Additionally, the protective effect is independent of the genetic background on which the Pklr mutations occurred. |
