Genetic variation in Mon1a affects protein trafficking and modifies macrophage iron loading in mice.

Published

Journal Article

We undertook a quantitative trait locus (QTL) analysis in mice to identify modifier genes that might influence the severity of human iron disorders. We identified a strong QTL on mouse chromosome 9 that differentially affected macrophage iron burden in C57BL/10J and SWR/J mice. A C57BL/10J missense allele of an evolutionarily conserved gene, Mon1a, cosegregated with the QTL in congenic mouse lines. We present evidence that Mon1a is involved in trafficking of ferroportin, the major mammalian iron exporter, to the surface of iron-recycling macrophages. Differences in amounts of surface ferroportin correlate with differences in cellular iron content. Mon1a is also important for trafficking of cell-surface and secreted molecules unrelated to iron metabolism, suggesting that it has a fundamental role in the mammalian secretory apparatus.

Full Text

Duke Authors

Cited Authors

  • Wang, F; Paradkar, PN; Custodio, AO; McVey Ward, D; Fleming, MD; Campagna, D; Roberts, KA; Boyartchuk, V; Dietrich, WF; Kaplan, J; Andrews, NC

Published Date

  • August 2007

Published In

Volume / Issue

  • 39 / 8

Start / End Page

  • 1025 - 1032

PubMed ID

  • 17632513

Pubmed Central ID

  • 17632513

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng2059

Language

  • eng

Conference Location

  • United States