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

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