Genetic variation in Mon1a affects protein trafficking and modifies macrophage iron loading in mice
Genetic variation in Mon1a affects protein trafficking and modifies macrophage iron loading in mice
复制标题
DOI：
10.1038/ng2059
复制
发表时间：
2007-08-01
期刊：
影响因子：
30.8
通讯作者：
Andrews, Nancy C.
中科院分区：
文献类型：
--
作者：
Wang, Fudi;Paradkar, Prasad N.;Andrews, Nancy C.
我们对小鼠进行了数量性状基因座（QTL）分析，以识别可能影响人类铁失调严重程度的修饰基因。我们在小鼠9号染色体上鉴定了一个强QTL，该QTL对C57 BL/10 J和SWR/J小鼠的巨噬细胞铁负荷有不同的影响。一个C57 BL/10 J错义等位基因的进化保守基因，Mon 1a，共分离的QTL在同源系小鼠。我们目前的证据表明，Mon 1a参与运输的ferroportin，主要的哺乳动物铁出口，铁回收巨噬细胞的表面。表面膜铁转运蛋白量的差异与细胞铁含量的差异相关。Mon 1a对于细胞表面和分泌的与铁代谢无关的分子的运输也是重要的，这表明它在哺乳动物分泌装置中具有基本作用。
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.