The equality of rats and mice
Iron deficiency is a problem that many people struggle with. A protein has now been identified that appears to be essential for iron absorption in the gut. This protein also represents the first mammalian iron transporter to be characterized at the molecular level. Within iron metabolism, it seems to play not just one, but several crucial roles. The discovery of the protein, called Nramp2, was made by scientists at the University at Buffalo and at the Children's Hospital in Boston, which is affiliated with Harvard University. The researchers hope their results will allow a better understanding of iron-deficiency anemia, the world's most widespread disease, which is particularly prevalent in underdeveloped countries. The results are published in the Proceedings of the National Academy of Sciences (February 3, 1998 Edition, Volume 95, Issue 3). Ways to treat hemochromatosis, or iron overload, the most common recessively inherited disease, may also be easier to find with this knowledge.
All cells in the body need iron to function, but the details of iron metabolism, particularly which proteins are specifically responsible for iron absorption in the gut and iron trafficking within cells, have long been a mystery to researchers. According to the scientists led by Michael Garrick from the University at Buffalo, their results show that the protein is involved in at least two, and probably three, important processes within iron metabolism.
The scientists found that it is the Nramp2 protein that actually takes up iron in the gastrointestinal tract. Later, when the iron has been absorbed by the body's cells, it must be transported to the mitochondria, where the heme in hemoglobin is produced.
According to the researchers, the results, as well as more recent work carried out at the University of Western Australia at Nedlands, suggest that the protein is also involved in a third type of iron transport, the non-transferrin bound iron transport. This type of transport comes into play when there is an excess of iron in the body: a condition that, if prolonged, can lead to abnormal iron deposits and he alth problems such as liver cirrhosis and heart disease.
The discovery of Nramp2 is based on research on two different animal models both suffering from iron deficiency anemia: the Belgrade rat and the microcytic mouse. Both types of animals are unable to properly absorb iron in the gastrointestinal tract or adequately assimilate it at the cellular level."It has taken 30 years since the discovery of these animal models to uncover the true cause of these anemias," Garrick commented.
In the mid-1990s, the University at Buffalo sequenced the rat genome and began to perform DNA analysis to find the gene encoding the protein responsible for the deficiency. At the same time, researchers at the Children's Hospital were engaged in DNA analysis of the microcytic mouse.
Garrick and the other scientists were themselves surprised by the comparison of their results: “We didn't know that we would come to the same conclusion. Not only does the same gene encode the same protein in both animals; it's also the same amino acid change that distinguishes the normal animal from a mutant." However, he cautioned against believing that Nramp2 is not the only iron transport protein controlling iron uptake."This protein doesn't answer all questions about iron transport," he said. "The remarkable thing is that it's involved in so many places."
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