Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene.
Although disorders of iron metabolism are prevalent, iron transport remains poorly understood. To address this problem, we undertook a positional cloning strategy to identify the causative mutation in mice with microcytic anaemia (mk). Homozygous mk/mk mice have microcytic, hypochromic anaemia due to severe defects in intestinal iron absorption and erythroid iron utilization. We report the identification of a strong candidate gene for mk, and suggest that the phenotype is a consequence of a missense mutation in Nramp2 (ref. 5), a previously identified gene of unknown function. Nramp2 is homologous to Nramp1, a gene activa in host defense. If Nramp2 is mk, as the cumulative evidence suggests, our findings have broad implications for the understanding of iron transport and resistance to intracellular pathogens.
Fleming
M D
MD
Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts, USA.
Trenor
C C
CC
Su
M A
MA
Foernzler
D
D
Beier
D R
DR
Dietrich
W F
WF
Andrews
N C
NC
D000595:Amino Acid Sequence; D000740:Anemia / Q000235:genetics*; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins; D004195:Disease Models, Animal; D005260:Female; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D007501:Iron; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2