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Staff writer

What accounts for the difference between boys and girls? A good answer for an introductory biology 101 exam is, perhaps, that a male has one X and one Y chromosome while a female has two X chromosomes.

But puzzlingly, this is not always true. There are people who have X and Y chromosomes but develop female characteristics. There also are XX males who develop testicles without a Y chromosome.

Recent research using gene technologies reveals that the key to sex determination depends not only on the X or Y chromosomes but also on genes carried by these chromosomes and by the other 22 pairs of chromosomes known as autosomes, and by the interaction of these genes. These genes act like switches, directing the embryo to develop as a male or a female — or sometimes both.

A team at the Mitsubishi Kasei Institute of Life Science has recently announced its discovery of a gene that causes male-to-female sex reversal in mice.

Using recombinant DNA techniques, the group, whose leader, Toru Higashinakagawa, has since become a professor at Waseda University, developed mutant mice by disrupting a gene called M33 — a component of chromosome 11, responsible for backbone development.

As expected, the mutant baby mice had abnormalities in their skeletons, but the team was puzzled by the fact that the gender ratio of the mutant mice appeared to be skewed in favor of females.

After dissecting the mice to examine their sex organs, the team members found, to their surprise, that none of the transgenic mice had developed normally as males. Of the 12 XY specimens, six had pairs of ovaries, three had indistinct reproductive organs, and three were hermaphrodites possessing both an ovary and a testicle.

In contrast, nearly all the XX mice had developed ovaries. “This gene is playing an important role in testes development,” said Yuko Kato-Fukui, a member of the research team. The findings were recently published in the journal Nature.

Since wide sections of the human and mouse genomes are similar, understanding the location of a sex-determining gene in mice may shed light on the role of the same gene in the human genome.

Although the M33 gene in humans is set on a different chromosome — number 17 as opposed to number 11 in mice — the findings may demystify the biological mechanism of sex determination and someday explain certain gender abnormalities.

Medical doctors have long recognized the importance of genetic factors through the study of patients with abnormal chromosomes. But it was not until sophisticated gene technologies were developed that researchers could pinpoint the genetic switches that decide whether an embryo becomes a boy or girl.

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