nm1054: a spontaneous, recessive, hypochromic, microcytic anemia mutation in the mouse.

Document Type

Article

Publication Date

2005

Keywords

Animals, Erythrocytes, Failure-to-Thrive, Genes-Recessive, Hematopoiesis, Infertility-Male, Iron, Linkage-(Genetics), Mice-Mutant-Strains, Protoporphyrins, Quantitative-Trait-Loci

First Page

3625

Last Page

3631

JAX Source

Blood 2005 Nov; 106(10):3625-31.

Abstract

Hypochromic, microcytic anemias are typically the result of inadequate hemoglobin production because of globin defects or iron deficiency. Here, we describe the phenotypic characteristics and pathogenesis of a new recessive, hypochromic, microcytic anemia mouse mutant, nm1054. Although the mutation nm1054 is pleiotropic, also resulting in sparse hair, male infertility, failure to thrive, and hydrocephaly, the anemia is the focus of this study. Hematologic analysis reveals a moderately severe, congenital, hypochromic, microcytic anemia, with an elevated red cell zinc protoporphyrin, consistent with functional erythroid iron deficiency. However, serum and tissue iron analyses show that nm1054 animals are not systemically iron deficient. From hematopoietic stem cell transplantation and iron uptake studies in nm1054 reticulocytes, we provide evidence that the nm1054 anemia is due to an intrinsic hematopoietic defect resulting in inefficient transferrin-dependent iron uptake by erythroid precursors. Linkage studies demonstrate that nm1054 maps to a genetic locus not previously implicated in microcytic anemia or iron phenotypes.

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