Insights into Blood Diseases from Worms and Mice

Results from genetic studies on microscopic worms extrapolated to a mouse model have revealed comparable genes that control early blood-cell development.

"We think we have found a way of efficiently studying how early blood-cell development is controlled and how gene defects in this process might lead to the development of blood diseases, including cancer,” said Dr. Scott Cameron, an assistant professor of pediatrics and molecular biology at the University of Texas Southwestern Medical Center (Dallas, USA).

The research was reported in the February 1, 2002, issue of Genes & Development (mouse study) and in the April 1, 2002, issue of Development (worm study). Dr. Cameron and colleagues from Harvard Medical School (Boston, MA, USA; www.med.harvard.edu) found that the pag-3 gene determines the fate of embryonic nerve cells in the microscopic worm Caenorhabditis elegans, a common soil nematode that was one of the first animals to have its genome sequenced. Worms with a mutation on the pag-3 gene did not develop the neuron cells that control forward and backward mobility.

"In the gene-deprived mice, I found a defect in blood formation exactly consistent with what was predicted by the worm work,” said Dr. Cameron. The mouse study revealed that when the Gfi-1b gene is muted in mice, their blood-stem cells fail to form red cells and platelets, causing mice embryos to die 11-12 days after fertilization. Related research has shown that knocking out the sister Gfi-1 gene prevents development of certain white blood cells, resulting in the mice dying shortly after birth. The blood-cell genetic defects in the mice were consistent with the defect identified in embryonic nerve cells in C elegans.

Dr. Cameron hopes to find comparable links to cancer tumors in humans, though he cautions that gene numbers, roles, mutations and other variants contrast sharply between the mouse and human genomes and raise major challenges for human-disease research. "But I know that, overall, I'm in the right genetic neighborhood,” he said.





Related Links:
Southwestern Medical Center
Harvard Medical School