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The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease
| Content Provider | Scilit |
|---|---|
| Author | Zohn, Irene E. Domenico, Ivana De Pollock, Andrew Ward, Diane McVey Goodman, Jessica F. Liang, Xiayun Sanchez, Amaru J. Niswander, Lee Kaplan, Jerry |
| Copyright Year | 2007 |
| Description | 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 Fpnffe 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 Fpnffe mouse represents the first mouse model of ferroportin disease. |
| Related Links | http://www.bloodjournal.org/content/bloodjournal/109/10/4174.full.pdf |
| Ending Page | 4180 |
| Page Count | 7 |
| Starting Page | 4174 |
| DOI | 10.1182/blood-2007-01-066068 |
| Journal | Blood |
| Issue Number | 10 |
| Volume Number | 109 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2007-05-15 |
| Access Restriction | Open |
| Subject Keyword | Research and Experimental Medicine Iron Missense Ferroportin Disease Mouse Mutation Protein Ffe Fpn Model Journal: Blood (Vol- 114, Issue- 10) |
| Content Type | Text |
| Resource Type | Article |
