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Newly identified gene cluster on mouse X chromosome provides insights into fertility

HOUSTON - Researchers at The University of Texas M. D. Anderson Cancer Center have discovered a cluster of 12 genes on the X chromosome in mice that appears to play an important role in reproduction. Reporting in the journal Cell, the scientists showed that knocking out just one of the genes resulted in reduced fertility in male mice.

The researchers found the cluster, which they dubbed the reproductive homeobox X-linked (or Rhox) genes, is selectively expressed in male and female reproductive tissues in adult mice.

Although the team cannot yet say that the discovery has any corollary to human biology, they already have found two versions of mouse Rhox genes on the human X chromosome - they are both expressed in human testes.

"Little is known about the causes of human infertility, and that is why we are acutely interested in the Rhox findings," says the study's lead investigator, Miles Wilkinson, Ph.D., a professor in the Department of Immunology. "Conversely, we are intrigued by the notion that these Rhox genes also might be useful tools for developing new contraceptive methods - either in men or women."

Wilkinson earlier had discovered the founding member of this Rhox gene cluster, the Pem gene - now called Rhox5 - which, while normally restricted in expression to reproductive tissues, is aberrantly expressed in a wide variety of tumors, including carcinomas, sarcomas and lymphomas.

Pem and the other Rhox genes belong to a class of so-called "homeobox" genes that all share a common stretch of DNA sequence. Homeobox genes are known to encode transcription factors - their job is to turn other genes on. But because most of the estimated 200 homeobox genes that have been identified in mammals are solitary, Wilkinson says it was quite a surprise to find that the Rhox genes were grouped together in a large cluster. The only other significantly sized homeobox gene cluster known is the Hox gene cluster, which was discovered more tha
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Contact: Nancy Jensen
nwjensen@mdanderson.org
713-792-0655
University of Texas M. D. Anderson Cancer Center
10-Feb-2005


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