RGD Reference Report - Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. - Rat Genome Database

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

Authors: Fleming, MD  Romano, MA  Su, MA  Garrick, LM  Garrick, MD  Andrews, NC 
Citation: Fleming MD, etal., Proc Natl Acad Sci U S A 1998 Feb 3;95(3):1148-53.
RGD ID: 729808
Pubmed: PMID:9448300   (View Abstract at PubMed)
PMCID: PMC18702   (View Article at PubMed Central)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypochromic anemia  IAGP 729808 RGD 
hypochromic anemia  ISOSlc11a2 (Rattus norvegicus)729808; 729808DNA:missense mutation:cds:p.G185R (human)RGD 
hypochromic anemia  IAGP 729808DNA:missense mutation:cds:p.G185R (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
abnormal iron homeostasis  IAGP 729808 RGD 
microcytic anemia  IAGP 729808 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Slc11a2  (solute carrier family 11 member 2)

Genes (Mus musculus)
Slc11a2  (solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2)

Genes (Homo sapiens)
SLC11A2  (solute carrier family 11 member 2)

Strains
BG  (anemic Belgrade)


Additional Information