A research team led by Leonard I. Zon, a Howard Hughes Medical Institute investigator at Children's Hospital Boston and Harvard Medical School, published its findings in the August 18, 2005, issue of the journal Nature. Zon and his colleagues in Boston collaborated on the studies with researchers from the University of Rochester Medical Center and the University of Utah School of Medicine.
The researchers began their studies hoping to learn why a zebrafish mutant known as shiraz (sir) failed to produce hemoglobin. The sir mutant zebrafish, which were first isolated by Zon and colleagues in the Tbingen Screen Consortium in Germany, intrigued the researchers because they die from anemia caused by lack of hemoglobin.
Over the years, Zon and his colleagues have discovered many zebrafish mutants that fail to make hemoglobin because of defects in iron metabolism. As they have teased out the causes of these defects, they have learned that the biochemical pathway involved in hemoglobin synthesis in zebrafish has been largely conserved over the 300 million years of evolution between fish and humans. According to Zon, the easily manipulable fish constitutes an excellent model organism for studying the regulation of heme formation.
In the current study, the researchers traced the hemoglobin defect to the gene for an enzyme known as glutaredoxin 5 (grx5). But the researchers found early on that the enzyme was not directly connected to hemoglobin production. "Nobody had worked on this gene in vertebrates before, but we found in the scientific literature that this gene in yeast was required for the production of iron-sulfur clusters in the mitochondria," said Zon. Iron-
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
17-Aug-2005