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Why Men Are That Way Kristen Philipkoski

3:00 a.m. 28.Oct.1999 PDT

SAN FRANCISCO -- Two X chromosomes do not necessarily make a female, according to recent research. A researcher at Baylor College of Medicine in Houston created a strain of transgenic mice whose offspring all turned out to be male, and every one of them had a double X chromosome. In other words, the X and Y chromosome combination may not determine male gender.

Instead, the new research suggests that male gender is determined by two genes, called Sry and Sox 9. "Females are 'repressed' males and males are 'repressed' females," said researcher Paul Overbeek, a professor of cell biology at Baylor. Sry is located on the Y chromosome and is the gene that researchers believe normally determines male gender. The researchers discovered that Sox 9 is the gene that regulates Sry expression. Researchers theorized that males either have some system for turning Sry on or that females have a system for turning it off, Overbeek said. In fact, his research proved both theories to be true. It turns out that the normal XX female does not express Sox 9 because it is suppressed, while the normal XY male gonad does express Sox 9.

"We eliminated the female ability to suppress Sox 9, and as a result of that, the XX mice expressed Sox 9 and that is sufficient to get the normal pathway of male development to occur, even in the complete absence of a Y chromosome," he said. Overbeek, who presented his findings last week at a late-breaking research session at the American Society of Human Genetics conference, believes the same holds true for humans.

The importance of Sry in determining gender was discovered by Dr. Robin Lovell-Badge of the National Institute for Medical Research in London about two years ago. "Although it was known to be the critical gene on Y, how it functioned was not yet so well established," Overbeek said. The male XX mice were sterile, which leads researchers to believe that germ cells -- those that make sperm -- are created by other genes located on the Y chromosome.

Overbeek created the transgenic mice by injecting them with a gene called tyrosinase minigene -- a gene that cures albinism. Overbeek had no inclination that their offspring would be males with two X chromosomes. "The original intention was to make mice that had interesting mutations," Overbeek said. "We just didn't know what we would end up with." Next, Overbeek plans to create the same type of transgenic mice intentionally and continue to study the mice.

There is a significant obstacle to the research, however. Since all of the offspring are male, the researchers can't breed them. "Our transgenic family is not a stable genetic system," Overbeek said. "You can't make females, so it's an evolutionary dead end." The work could answer a long-pondered question: Who came first, Adam or Eve? "We don't know which came first even from our research, but the system is set up so that the pathways for male or female development are essentially encoded completely in the genome of the male and female both. One simple genetic switch sends the developmental program in one direction or another," Overbeek said. "Males and females are really very much genetically the same."

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