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The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease.

Blood | May 15, 2007

http://www.ncbi.nlm.nih.gov/pubmed/17289807

Ferroportin disease is caused by mutation of one allele of the iron exporter ferroportin (Fpn/IREG1/Slc40a1/MTP1). All reported human mutations are missense mutations and heterozygous null mutations in mouse Fpn do not recapitulate the human disease. Here we describe the flatiron (ffe) mouse with a missense mutation (H32R) in Fpn that affects its localization and iron export activity. Similar to human patients with classic ferroportin disease, heterozygous ffe/+ mice present with iron loading of Kupffer cells, high serum ferritin, and low transferrin saturation. In macrophages isolated from ffe/+ heterozygous mice and through the use of Fpn plasmids with the ffe mutation, we show that Fpn(ffe) acts as a dominant negative, preventing wild-type Fpn from localizing on the cell surface and transporting iron. These results demonstrate that mutations in Fpn resulting in protein mislocalization act in a dominant-negative fashion to cause disease, and the Fpn(ffe) mouse represents the first mouse model of ferroportin disease.

Pubmed ID: 17289807 RIS Download

Mesh terms: Animals | Base Sequence | Cation Transport Proteins | Cells, Cultured | DNA Mutational Analysis | Genes, Dominant | Humans | Iron | Iron Metabolism Disorders | Macrophages | Mice | Mice, Inbred C3H | Mice, Inbred C57BL | Mice, Mutant Strains | Mutation | Protein Transport

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Associated grants

  • Agency: NIDDK NIH HHS, Id: DK070 947
  • Agency: NICHD NIH HHS, Id: F32-HD08 605
  • Agency: NCI NIH HHS, Id: T32CA8608604

Mouse Genome Informatics (Data, Gene Annotation)

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