Forward genetics used to identify new gene Mon1a with critical role in controlling macrophage iron metabolism and iron recycling from erythrocytes.
A recent study used a forward genetics approach to identify a new gene whose protein product controls erythrocyte iron recycling mediated through macrophages in the spleen. Initially the investigators found a genetic region on chromosome 9 accounting for one third of the variation in spleen iron level in mice. Additional approaches to narrow the genomic region identified the gene Mon1a, which codes for a protein that acts as a novel regulator of spleen iron release. Cell-based studies showed that Mon1a is necessary for vesicular trafficking of proteins, including the iron-export protein ferroportin, to the macrophage cell membrane. The forward genetics approach, which has currently only been used sparingly by the nutrition research community, offers a powerful and unbiased approach to identifying genes important in nutritional metabolism.
Department of Foods and Nutrition, and Center for Gene Environment Interactions, Purdue University, West Lafayette, Indiana 47906-2059, USA.
Rebecca A
RA
McCreedy
James C
JC
Fleet
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / 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; D012157:Mononuclear Phagocyte System / Q000502:physiology; D009752:Nutritional Status / Q000502:physiology; D021381:Protein Transport; D040641:Quantitative Trait Loci; D034741:RNA, Small Interfering; D013154:Spleen / Q000737:chemistry; D000098742:Ferroportin
D002352:Carrier Proteins; D027682:Cation Transport Proteins; C522811:Mon1a protein, mouse; D034741:RNA, Small Interfering; D000098742:Ferroportin; D007501:Iron