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When One Gene Has Two Roles, Its Second Function May Be Missed

In a surprising finding that underscores the difficulty in understanding how genes guide the developing mammalian embryo, an international team of scientists has found that the same master gene that controls development of all of the body's blood cells is later activated in other cells of the embryo to form the genitourinary tract.

Disorders in the gene's function, particularly in the genitourinary tract, where it was not previously known to act, may underlie some human diseases.

The researchers, from Northwestern University, Harvard Medical School and the University of Tsukuba in Japan, claim that the finding points to one obvious pitfall to a powerful experimental technique in mice that scientists have used for a decade to try to unravel the genetics of mammalian fetal development: Simply, if a single gene has more than one vital function, the first lethal defect will abort the embryo before the second defect manifests.

"The mouse embryo may be lost early in gestation before the second defect can be revealed," says J. Douglas Engel, Owen L. Coon Professor of Biochemistry, Molecular Biology and Cell Biology at Northwestern, who directed the research. "We may miss additional roles for a gene we're studying, unless we can somehow circumvent the embryologically disasterous effects of the first missing function."

Engel and his colleagues found a way to circumvent early abortion due to a missing function from a known vital gene, unmasking a previously unknown second role later in fetal development. The results are reported in the Nov. 16 issue of the journal of the European Molecular Biology Organization.

Engel and his co-workers were studying a master signal molecule called GATA-2 that turns on other genes necessary to set embryonic precursor cells along the pathway that will give rise to all the various types of blood cells in a newborn mouse. By using a now-common technique called gene targeting, they created mice that were missing one of thei
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Contact: Bill Burton
b-burton@nwu.edu
847-491-3115
Northwestern University
12-Nov-1998


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