Mouse Gene Accounts for Blood Abnormalities as Well as Parkinson's Symptoms

Search Begins For Gene's Role In Human Illnesses

Mice found in a previous study to develop a Parkinson's-like deterioration when deprived of a gene for iron metabolism were also found to develop anemia and signs of a rare skin condition, according to a follow up study by researchers at the National Institute of Child Health and Human Development of the National Institutes of Health.

The researchers believe that the gene may play a role in human diseases and are now searching for people with Parkinson's disease-like symptoms and anemia that has certain characteristics.

"This study provides additional clues that may contribute to our understanding of neurodegenerative disorders that appear to involve iron metabolism," said Duane Alexander, M.D., Director of the NICHD.

The study was published online in the journal "Blood".

To conduct the study, the researchers developed mice lacking the gene that makes iron regulatory protein 2 (IRP), which helps to regulate the amount of iron in cells, explained the study's senior author, Tracey A. Rouault, M.D., of NICHD's Section on Human Iron Metabolism. The researchers originally reported in the February 2001 issue of "Nature Genetics" that mice lacking the gene for IRP2 develop iron deposits in specific parts of the brain and develop symptoms resembling Parkinson's disease.

In the current study, the researchers also learned that the mice developed anemia and blood abnormalities sometimes seen in people with a rare condition known as erythropoietic protoporphyria.

Because the genetics of both kinds of diseases are not completely understood, Dr. Rouault and her coworkers believe that some of the people with either Parkinson's-like symptoms or erythropoietic protoporphyria might have an error involving the IRP2 gene.

The researchers currently are testing drugs to treat the neurological symptoms in the IRP 2-deficient mice. If they can identify human beings with faulty IRP 2 functioning, it is possible that these people might participate in studies of such drug treatments.

Dr. Rouault explained that IRP 2 governs the actions of various other proteins involved in iron metabolism. These include transferrin receptor, which transports iron into the cell; ferritin, which stores iron safely away from the cell's internal machinery; and iron exporters, which ferry iron out of the cell.

The researchers developed the mice by using a method known as "knockout technology," to permanently remove the gene. In the original study, the researchers learned that these mice developed normally at first, and then progressively had difficulty walking and moving. Examination of their brains revealed tiny clumps of iron in brain areas. These mice also had high blood levels of the iron storage protein ferritin. The researchers think that the loss of function seen in the mice resembles the loss of function seen in people with Parkinson's disease and Multiple System Atrophy (also known as Parkinson's Plus).

In the current study, the researchers learned that the mice also have high blood levels of a compound known as protoporphyrin IX. This compound is converted into heme, the compound that allows red blood cells to carry oxygen to the tissues. The mice also have microcytic anemia-abnormally small red blood cells.

To conduct the next phase of their research, Dr. Rouault and her coworkers are seeking patients who have Parkinson's-like symptoms together withanemia. They're especially interested in hearing from people with:

  • Parkinson's disease
  • Multiple Systems Atrophy (formerly known as Olivopontocerebellar Atrophy)
  • Or another neurodegenerative disease with Parkinson's-like neurological
  • deterioration.

With positive test results for:

  • High levels of protoporphyrin IX
  • High serum ferritin levels
  • And microcytic anemia (abnormally small red blood cells)

Dr. Rouault added that it's possible some people with erythropoietic protoporphyria may have a mutation in iron regulatory protein 2. She would be interested in hearing from people with this condition as well. People with erythropoetic protoporphyria have skin that is abnormally sensitive to light and may experience a severe burn from exposure to sunlight. They may also experience irritated, itchy skin and suffer from frequent skin sores.

To contact Dr. Rouault about participating in a study, call 301-496-6368 or send her an e-mail message at


The NICHD is part of the National Institutes of Health (NIH), the biomedical research arm of the federal government. NIH is an agency of the U.S. Department of Health and Human Services. The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation.

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