| First Author | Zohn IE | Year | 2007 |
| Journal | Blood | Volume | 109 |
| Issue | 10 | Pages | 4174-80 |
| PubMed ID | 17289807 | Mgi Jnum | J:118592 |
| Mgi Id | MGI:3699946 | Doi | 10.1182/blood-2007-01-066068 |
| Citation | Zohn IE, et al. (2007) The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease. Blood 109(10):4171-80 |
| abstractText | 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. |
