Studies Of Genes In Mice And Common Worm May Accelerate Research On Blood Diseases, Cancers

“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 and a pediatric oncologist who joined UT Southwestern in July.

His research, reported in the April 8 issue of the journal Development, found that the pag-3 gene determines the fate of embryonic nerve cells in the microscopic worm Caenorhabditis elegans, a common soil nematode that became the first animal to have its genome sequenced.

“I showed that the gene in the worm, C. elegans, determines what the daughter cells will become after a cell division in the nervous system,” Cameron said.

On the basis of what he and his colleagues learned from the worm, they collaborated in a subsequent study to knock out the counterpart mouse genes, which perform similar cell-determination functions but in the blood cells.

“In the gene-deprived mice, I found a defect in blood formation exactly consistent with what was predicted by the worm work,” said Cameron, the principal investigator who collaborated with Dr. Stuart Orkin’s lab at the Howard Hughes Medical Institute at Harvard Medical School and with Children’s Hospital, both in Boston. The mice study was published first, in the February issue of Genes & Development.

His pag-3 gene study found that a mutation resulted in a failure of the worm to develop neuron cells controlling forward and backward mobility. “Worms with the mutated pag-3 do not move well,” Cameron said.

The worm’s uniform genetic patterns from egg to mature adult provide clues to uncovering the counterpart but more complex genetic patterns in mice, and mice patterns are closely akin to the still more complex human genetic mechanisms, he said.

Cameron’s later 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 whi