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

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...

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Published inNature genetics Vol. 39; no. 8; pp. 1025 - 1032
Main Authors Andrews, Nancy C, Wang, Fudi, Paradkar, Prasad N, Custodio, Angel O, McVey Ward, Diane, Fleming, Mark D, Campagna, Dean, Roberts, Kristina A, Boyartchuk, Victor, Dietrich, William F, Kaplan, Jerry
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.08.2007
Nature Publishing Group
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Summary: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.
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ISSN:1061-4036
1546-1718
DOI:10.1038/ng2059