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, Andrews Nancy C
Division of Hematology/Oncology, Children's Hospital Boston, Boston, Massachusetts, 02115 USA.
Nat Genet. 2007 Aug;39(8):1025-32. doi: 10.1038/ng2059. Epub 2007 Jul 15.
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.
我们在小鼠中进行了数量性状基因座（QTL）分析，以鉴定可能影响人类铁紊乱严重程度的修饰基因。我们在小鼠9号染色体上鉴定出一个强QTL，它对C57BL/10J和SWR/J小鼠的巨噬细胞铁负荷有不同影响。进化保守基因Mon1a的一个C57BL/10J错义等位基因与同源小鼠品系中的QTL共分离。我们提供的证据表明，Mon1a参与了主要的哺乳动物铁输出蛋白铁转运蛋白向铁循环巨噬细胞表面的运输。表面铁转运蛋白数量的差异与细胞铁含量的差异相关。Mon1a对于与铁代谢无关的细胞表面和分泌分子的运输也很重要，这表明它在哺乳动物分泌装置中具有重要作用。
