When mice lack this gene, their eggs do not develop and they are infertile, said Dr. Aleksandar Rajkovic, a BCM assistant professor of obstetrics and gynecology. Their condition resembles that of women who have ovarian failure, he said. Studying these mice may provide important clues about mechanisms of ovarian failure. It may also in the future enable genetic control of mammalian reproductive life-span and improve our ability to regulate fertility and generate mature eggs in vitro.
In a report in today ™s issue of the journal Science, Rajkovic and his colleagues describe the actions of Nobox, which is a homeobox gene capable of regulating others. They showed that in mice, a lack of the Nobox gene resulted in the loss of activity of other genes that are active only in the oocytes.
Nobox appears to govern the activity of genes crucial to the development of follicles, which hold the immature eggs cells or oocytes. These follicles are supposed thicken as the mouse develops. Without Nobox, the follicles do not develop and the oocytes deteriorate.
The preparation for early embryogenesis (formation of embryos) begins with folliculogenesis (formation of follicles), said Rajkovic. When this gene is deleted, there is no folliculogenesis and no oocytes.
Others who participated in the research include Drs. Stephanie A. Pangas, Daniel Ballow, Nobuhiro Suzumori and Martin M. Matzuk.
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To further demonstrate the defensive importance of the clotting system, the researchers administered a substance derived from snake venom that degrades another clotting protein, fibrinogen, and found that it too greatly increased the mice's mortality from this streptococcus infection.
To Ginsburg, who has spent much of his career studying the genetics of blood clotting and clotting disorders such as hemophilia, the findings highlight an evolutionary arms race between bacteria and humans.
"Clearly, if we could mutate our plasminogen so it still worked, yet was resistant to a bacterial streptokinase, it would give us an advantage," Ginsburg said. "But then the bacteria could mutate their streptokinase to keep up."
The findings also suggest that subtle variations in plasminogen genes among humans may explain why some people are more susceptible to strep infections than others.
Ginburg's laboratory is now exploring the genetic variations in the blood-clotting system that might affect risk factors for infection. "Although this is speculation at this point, it might ultimately be possible to tailor treatment of infections to the pattern of genetic variability in clotting genes or other pathogenicity factors," Ginsburg said.
The research, being published in the Aug. 26 issue of the journal Science, also included colleagues at Lund University in Sweden.
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