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 Hunting pathogens at full force
22.03.2017 | Helmholtz-Zentrum für Infektionsforschung

nachricht A 155 carat diamond with 92 mm diameter
22.03.2017 | Universität Augsburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Pulverizing electronic waste is green, clean -- and cold

22.03.2017 | Materials Sciences

Astronomers hazard a ride in a 'drifting carousel' to understand pulsating stars

22.03.2017 | Physics and Astronomy

New gel-like coating beefs up the performance of lithium-sulfur batteries

22.03.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>