Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

11.02.2005


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 than 20 years ago. "We also were excited to find that all the genes in the Rhox gene cluster are selectively expressed in male and female reproductive tissue in adult mice," Wilkinson says. "This suggests the possibility that this gene cluster encodes a set of proteins devoted exclusively to regulating reproduction."

"What is perhaps even more intriguing," he says, "is their colinear expression pattern - in other words, the position of the Rhox genes on the X chromosome precisely correlates with their expression pattern. The first gene in the cluster, Rhox1, is expressed first during testis development, the Rhox2 is expressed second, and so on. This unique expression pattern has implications for the evolution, regulation and function of the X-linked Rhox genes."

Knowing that, the researchers tested what would happen if they "knocked out" just one of the Rhox genes in male mice. They found that an engineered mouse that lacked a functioning Rhox5 gene exhibited reduced sperm production, as well as sperm motility and fertility.

Wilkinson’s group also found that most of the 12 Rhox genes, including Rhox5, are expressed in Sertoli cells, the "nurse" cells within testes that are in direct contact with the germ cells that produce sperm. They also found that at least five of the Rhox genes are activated by testosterone, the hormone essential for the production of sperm. "This was interesting because it has long been a mystery how testosterone elicits the formation of sperm in the testis," he says. "Based on our findings, we propose that testosterone binds to its receptor on Sertoli cells, which causes Rhox genes to be activated, which then turns on a genetic cascade that affects the neighboring germ cells, pushing them to mature and become sperm."

"Another thing that some Rhox genes could be doing is regulating the production of proteins within Sertoli cells that allow the neighboring germ cells to survive," Wilkinson says. "If you knock out Rhox5, many more germ cells die than would normally."

The researchers do not know why the Rhox genes are on the X chromosome but they find it intriguing, as the X chromosome is one of the "sex chromosomes." Female mammals have two X chromosomes, while males only have one. Wilkinson speculates that the Rhox genes occupy a position on the X chromosome because of unique evolutionary forces driving many reproduction genes to be located on this particular chromosome.

Another interesting aspect of the Rhox genes is that there are at least 12 in mice but only two so far have been identified in humans. Wilkinson says that the existence of a large gene cluster devoted to reproduction in mice, but not perhaps in humans, "is consistent with the greater reproductive capacity of rodents."

The researchers are in the process of knocking out additional genes in the Rhox gene cluster to examine their role in both male and female reproduction in mice. They also plan to search for additional human Rhox genes once the human X chromosome is fully mapped and sequenced.

The study was funded by the National Institutes of Health. Co-authors include, from M. D. Anderson, first author James Maclean II, Ph.D., Mingang Chen, Ph.D., Chad Wayne, Ph.D., Shirley Bruce, Ph.D., Manjeet Rao, Ph.D., and Marvin Meistrich, Ph.D. Co-author Carol Macleod, Ph.D., from the School of Medicine at the University of California at San Diego, contributed the Rhox5 knock-out mouse.

Nancy Jensen | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>