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Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport.

Publication ,  Journal Article
Fleming, MD; Romano, MA; Su, MA; Garrick, LM; Garrick, MD; Andrews, NC
Published in: Proceedings of the National Academy of Sciences of the United States of America
February 1998

The Belgrade (b) rat has an autosomal recessively inherited, microcytic, hypochromic anemia associated with abnormal reticulocyte iron uptake and gastrointestinal iron absorption. The b reticulocyte defect appears to be failure of iron transport out of endosomes within the transferrin cycle. Aspects of this phenotype are similar to those reported for the microcytic anemia (mk) mutation in the mouse. Recently, mk has been attributed to a missense mutation in the gene encoding the putative iron transporter protein Nramp2. To investigate the possibility that Nramp2 was also mutated in the b rat, we established linkage of the phenotype to the centromeric portion of rat chromosome 7. This region exhibits synteny to the chromosomal location of Nramp2 in the mouse. A polymorphism within the rat Nramp2 gene cosegregated with the b phenotype. A glycine-to-arginine missense mutation (G185R) was present in the b Nramp2 gene, but not in the normal allele. Strikingly, this amino acid alteration is the same as that seen in the mk mouse. Functional studies of the protein encoded by the b allele of rat Nramp2 demonstrated that the mutation disrupted iron transport. These results confirm the hypothesis that Nramp2 is the protein defective in the Belgrade rat and raise the possibility that the phenotype shared by mk and b animals is unique to the G185R mutation. Furthermore, the phenotypic characteristics of these animals indicate that Nramp2 is essential both for normal intestinal iron absorption and for transport of iron out of the transferrin cycle endosome.

Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

February 1998

Volume

95

Issue

3

Start / End Page

1148 / 1153

Related Subject Headings

  • Transferrin
  • Sequence Alignment
  • Rats
  • Mutation
  • Molecular Sequence Data
  • Mice
  • Membrane Proteins
  • Iron-Binding Proteins
  • Iron
  • Glycine
 

Citation

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Fleming, M. D., Romano, M. A., Su, M. A., Garrick, L. M., Garrick, M. D., & Andrews, N. C. (1998). Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proceedings of the National Academy of Sciences of the United States of America, 95(3), 1148–1153. https://doi.org/10.1073/pnas.95.3.1148
Fleming, M. D., M. A. Romano, M. A. Su, L. M. Garrick, M. D. Garrick, and N. C. Andrews. “Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport.Proceedings of the National Academy of Sciences of the United States of America 95, no. 3 (February 1998): 1148–53. https://doi.org/10.1073/pnas.95.3.1148.
Fleming MD, Romano MA, Su MA, Garrick LM, Garrick MD, Andrews NC. Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proceedings of the National Academy of Sciences of the United States of America. 1998 Feb;95(3):1148–53.
Fleming, M. D., et al. “Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport.Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 3, Feb. 1998, pp. 1148–53. Epmc, doi:10.1073/pnas.95.3.1148.
Fleming MD, Romano MA, Su MA, Garrick LM, Garrick MD, Andrews NC. Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proceedings of the National Academy of Sciences of the United States of America. 1998 Feb;95(3):1148–1153.
Journal cover image

Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

February 1998

Volume

95

Issue

3

Start / End Page

1148 / 1153

Related Subject Headings

  • Transferrin
  • Sequence Alignment
  • Rats
  • Mutation
  • Molecular Sequence Data
  • Mice
  • Membrane Proteins
  • Iron-Binding Proteins
  • Iron
  • Glycine