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 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.
Wang
Fudi
F
Division of Hematology/Oncology, Children's Hospital Boston, Boston, Massachusetts, 02115 USA.
Paradkar
Prasad N
PN
Custodio
Angel O
AO
McVey Ward
Diane
D
Fleming
Mark D
MD
Campagna
Dean
D
Roberts
Kristina A
KA
Boyartchuk
Victor
V
Dietrich
William F
WF
Kaplan
Jerry
J
Andrews
Nancy C
NC
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D033481:Chromosomes, Mammalian; D003433:Crosses, Genetic; D005260:Female; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D021381:Protein Transport; D040641:Quantitative Trait Loci; D034741:RNA, Small Interfering; D000098742:Ferroportin
D002352:Carrier Proteins; D027682:Cation Transport Proteins; C522811:Mon1a protein, mouse; D034741:RNA, Small Interfering; D000098742:Ferroportin; D007501:Iron