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
"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
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
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 with anemia. They're especially interested
in hearing from people with:
- Parkinson's disease,
- Multiple Systems Atrophy (formerly known as Olivopontocerebellar
- Or another neurodegenerative disease with Parkinson's-like
With positive test results for:
- High levels of protoporphyrin IX
- High serum ferritin levels
- And microcytic anemia (abnormally small red blood
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
To contact Dr. Rouault about participating in a study,
call 301-496-6368 or send her an e-mail message at firstname.lastname@example.org
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.