Iron Absorption Controlled by Liver Gene
Liver-specific deletion causes hemochromatosis-like symptoms in mice
THURSDAY, Dec. 8 (HealthDay News) -- Mice with a liver-specific deletion of the tumor suppressor gene SMAD4 develop symptoms of iron-overload similar to the human disease hemochromatosis, according to a report in the December issue of Cell Metabolism.
Chu-Xia Deng, from the National Institute of Diabetes and Digestive and Kidney Diseases, and colleagues set out to understand SMAD4's role in liver development and maintenance by specifically deleting the gene only in this organ. Loss of SMAD4 function has been linked to multiple forms of cancer, including the pancreas, colon and lung.
While the mice initially appeared normal and did not develop cancer, by 10 months the mice had lost weight and muscle mass, and had rough-looking fur. Tissue analysis showed iron buildup in their liver as well as pancreas and kidneys.
This surprising finding of SMAD4's control over liver metabolism was supported by gene expression and activity analysis, which showed a reduction in hepcidin function, a regulator of iron absorption in the intestine, in the SMAD4 mice. "Our work not only creates a new animal model for hemochromatosis, but also clearly indicates that the liver is a physiological center for regulation of iron homeostasis," the authors conclude.