Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-4-21
pubmed:abstractText
The recombinant congenic mouse strains AcB55 and AcB61 are extremely resistant to malaria (Plasmodium chabaudi AS) despite the presence of susceptibility alleles at the known Char1/Char2 resistance loci. Resistance in AcB55 and AcB61 is controlled by a locus on chromosome 3 (Char4) shown to be allelic with or tightly linked to a loss-of-function mutation in pyruvate kinase (Pklr). AcB55 and AcB61 show important splenomegaly prior to infection caused by the expansion of the red pulp, and display histological signs of extramedullary erythropoiesis in the liver. Examination of splenic cell populations by flow cytometry demonstrates elevated numbers of TER119-positive erythroid precursor cells (>30% of total spleen cells), while RNA expression studies show elevated expression of erythrocyte-specific transcripts such as globin, transferrin receptor, and Nramp2/Slc11a2 in the spleen of both strains. Hematological profiling in both strains is consistent with the presence of anemia as evidenced by low total erythrocyte counts, decreased hemoglobin, as well as abnormally high numbers of circulating reticulocytes (15-20%). These results strongly suggest that the mutant Pklr allele (Pklr(269A)) of AcB55/61 strains causes hemolytic anemia compensated by constitutive erythropoiesis, which in turn protects the mice against P. chabaudi infection. The possible molecular basis of the Pklr protective effect is discussed and is under current investigation in these two strains.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1466-4879
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
168-75
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15029238-Anemia, Hemolytic, pubmed-meshheading:15029238-Animals, pubmed-meshheading:15029238-Cation Transport Proteins, pubmed-meshheading:15029238-Disease Models, Animal, pubmed-meshheading:15029238-Erythrocytes, pubmed-meshheading:15029238-Erythropoiesis, pubmed-meshheading:15029238-Genetic Predisposition to Disease, pubmed-meshheading:15029238-Globins, pubmed-meshheading:15029238-Immunity, Innate, pubmed-meshheading:15029238-Iron-Binding Proteins, pubmed-meshheading:15029238-Malaria, pubmed-meshheading:15029238-Mice, pubmed-meshheading:15029238-Mice, Congenic, pubmed-meshheading:15029238-Mice, Inbred A, pubmed-meshheading:15029238-Mice, Inbred C57BL, pubmed-meshheading:15029238-Phenotype, pubmed-meshheading:15029238-Plasmodium chabaudi, pubmed-meshheading:15029238-Pyruvate Kinase, pubmed-meshheading:15029238-Receptors, Transferrin, pubmed-meshheading:15029238-Splenomegaly
pubmed:year
2004
pubmed:articleTitle
Phenotypic expression of pyruvate kinase deficiency and protection against malaria in a mouse model.
pubmed:affiliation
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't