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 Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>