 
|
Researchers at the Transgenic Mouse Facility at the School of Medicine have confirmed the causative role of the gene mutation responsible for hereditary hemochromatosis (HH), also known as iron overload disease. The gene discovery was confirmed after researchers created a mouse model for the mutation.
The study shows that the gene is involved in the regulation of iron overload and that mutations in this gene are responsible for HH. Hemochromatosis is the most commonly inherited disease among Caucasians. It is estimated that as many as one in eight individuals of Northern European descent are carriers of the gene mutation. If not treated, HH can lead to cirrhosis of the liver, diabetes, and heart failure.
"In collaboration with Dr. Bruce Bacon in the department of medicine, who was a key player in the discovery of the candidate gene in HH patients, we did several studies here to understand the biology of the gene mutation," said William S. Sly, M.D., Alice A. Doisy Professor and chairman of the Edward A. Doisy Department of Biochemistry and Molecular Biology. "We decided the real test of whether this candidate gene mutation was the underlying defect in HH would be to make a similar kind of mutation in the mouse and see if the mouse developed the same disease humans do."
Dr. Xiao Yan Zhou, director of the Transgenic Mouse Facility, introduced a similar gene mutation into the mice. They were then bred and became carriers of the gene. The offspring of carrier mice, which had two copies of what is called the "knockout gene," developed the disease by the age of 10 weeks.
"That turned out to be the evidence we needed to prove the hypothesis that this was the right gene," Sly said.
In addition, Sly said the knockout gene provides an animal model to study the basic, fundamental defect underlying the disease and possibly to try different methods of treatment. The company working on the gene discovery, Progenitor Inc. of Menlo Park, Calif., is interested in using the mouse model as a means to develop drug treatment for HH. In addition, they have developed a screening test to detect the mutation.
The knockout mouse will lead to future studies of the scientific and medical nature of the disease and will provide opportunities to evaluate therapeutic strategies for prevention or correction of iron overload.
This research also may be beneficial for the large number of people worldwide who have iron overload because of anemia.Sickle-cell patients, for example, absorb too much iron and develop iron storage. The only true method of treatment right now is a bone marrow transplant.
"This won't lead to a treatment for the anemia," Sly said. "But it may lead to a way to understand and deal with the iron overload."
  |