Now researchers at UT Southwestern Medical Center have added another experimental research animal to the scientific stable: the rat.
In a new study appearing in the June issue of Nature Methods, UT Southwestern researchers detail how they created 35 new rat "lines," with each type of animal harboring mutations in specific genes. More than half of these mutated genes are associated with biological processes linked to human diseases, including cancer, diabetes, Alzheimer's disease, aberrant circadian rhythms and mental illness.
Dr. Kent Hamra, assistant professor of pharmacology and lead author of the study, said the ability to easily, reliably and inexpensively produce genetically modified rats offers tremendous potential for biomedical research for even small laboratories with limited resources. For example, compared to the mouse, the rat is a larger, more intelligent animal; it is often better for biochemistry, pharmacology and physiology studies; and its behavior often is more in tune with that of humans.
"Our studies are focused on sperm-cell biology and fertility genes, but ultimately, we think other scientists will utilize these relatively simple, cost-effective techniques to generate genetically altered rats for use in experiments related to human disease," Dr. Hamra said.
One of the keys to producing the mutated rats was a novel technique Dr. Hamra and his colleagues in the Cecil H. and Ida Green Center for Reproductive Biology Sciences at UT Southwestern developed five years ago to prevent rat sperm stem cells – sperm precursor cells – from differentiating, or changing, permanently into sperm.
"Getting sperm stem cells to grow in culture was a huge step," Dr. Hamra said. "In these new experiments, we took the next step and genetically modified these precursor cells in culture, selected them for mutations and introduced the cells into the testes of a sterile male rat."
The animal produces genetically altered sperm, resulting in mutant offspring that can be used for biomedical research.
Other methods have been used in limited ways to produce altered rats, but those methods do not involve manipulating stem cells in culture. In addition, genetic methods typically used to modify mice employ the use of the rodents' embryonic stem cells, and these methods have not worked well in other mammals, including the rat, Dr. Hamra said.
The latest work, he said, is proof-of-principle that genetic mutations introduced into mammalian stem cells from species other than mice can indeed be preselected for in culture and passed on to offspring.
Another key to Dr. Hamra's success in producing genetically altered rats came from two co-authors on the study, Drs. Zsuzsanna Izsvák and Zoltán Ivics of the Max-Delbruck Center for Molecular Medicine in Berlin. They developed a method to trigger mutations in specific areas of mammalian DNA. The method relies on deploying a segment of DNA called a transposon, which, when introduced into an organism's DNA, "jumps" randomly around the genome, creating mutations along the way.
"A transposon is nature's simplified way of cutting and pasting DNA in and out of the genome," Dr. Hamra said.
The researchers in Germany developed ways to harness the power of transposons for mammalian species and to control precisely where and how in a given genome they do their mutagenic "hopping." For example, a transposon can be limited to producing mutations only in an area of the genome where scientists think a disease-related gene resides.
In addition to producing actual animals, Dr. Hamra and his colleagues also are now using the transposon method to generate complex libraries of sperm stem cells harboring various genetic mutations. To date, they have about 100 cell lines with different mutations stored frozen in their labs.
"Because testes of a single rat can support sperm production from thousands of individual stem cells and because rats are so prolific, these libraries open the door to an economic strategy for high-throughput mutagenesis screens in the rat," Dr. Hamra said.
Other UT Southwestern pharmacology researchers involved in the work are research intern James Shirley, research assistant Heather Powell and research scientist Karen Chapman.
The National Institutes of Health, the Bundesministerium for Bildung und Forschung, and UT Southwestern's Cecil H. and Ida Green Center for Reproductive Biology Sciences funded the research.
This news release is available on our World Wide Web home page at http://www.utsouthwestern.edu/home/news/index.html
To automatically receive news releases from UT Southwestern via e-mail, subscribe at www.utsouthwestern.edu/receivenews
Amanda Siegfried | EurekAlert!
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
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...
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...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine