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.