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Unexpected link between gene in liver and iron overload

A new study in the December Cell Metabolism reveals an unexpected connection between a tumor suppressor gene in the liver and the normally careful control over the amount of iron absorbed from the diet. The surprising finding demonstrates a critical role for the liver in iron metabolism. The discovery also suggests a new avenue for the treatment of hereditary hemochromatosis, an iron-overload disease that is one of the most common genetic disorders among Caucasians, according to researchers.

Chu-Xia Deng, from the National Institute of Diabetes and Digestive and Kidney Diseases, and his colleagues report that mice lacking the SMAD4 gene in the liver only suffer from a toxic buildup of iron, particularly in their liver, kidneys, and pancreas--symptoms similar to those exhibited by humans with hemochromatosis. In other respects, the animals appeared remarkably normal, the researchers found.

"Unexpectedly, the liver-specific knockout of SMAD4 does not have a major impact on liver development; instead it results in a dramatic accumulation of iron in the liver of mutant mice," Deng said. "In addition, several other organs with intact SMAD4, including pancreas, kidney, eye, and brain, also exhibit accumulation of iron starting from 2 months of age.

"Our work not only creates a new animal model for the study of hemochromatosis but also clearly indicates that the liver is a physiological center for regulation of iron homeostasis," he added.

Iron is an essential nutrient found in many foods, particularly in red meat and iron-fortified bread and cereal. In the body, iron becomes part of hemoglobin, a molecule in the blood that transports oxygen from the lungs to all body tissues. Iron deficiency results in anemia, whereas iron overload leads to organ and tissue damage.

Symptoms of hemochromatosis, the most common iron-overload disease, can include bronzed skin, enlarged liver, diabetes, and abnormalities of the pancreas and joints. Fre
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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
6-Dec-2005


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