Genetically modified rats with human diseases
For more than two decades, mice have been the only mammal whose genetically modified lines have been widely used as models of various human diseases and traits in biomedical research.
Despite the enormous benefits of mouse models, there is a need in the scientific community to use other, more complex animals, for example, rats, as experimental models. Recently, researchers obtained the first line of rats with simulated Alzheimer's disease. And in the article "Generating knockout rats by transposon mutagenesis in spermatogonial stem cells", published in the June issue of the journal Nature Methods, scientists at the University of Texas Southwestern Medical Center, working under the guidance of Dr. Kent Hamra, described in detail the creation of 35 more lines of genetically modified rats, the genotype of each of which carries a specific mutation. More than half of the mutation-carrying genes are associated with biological processes involved in the pathogenesis of various human diseases, including cancer, diabetes, Alzheimer's disease, heart rhythm disorders and mental disorders.
According to Dr. Hamr, an easy, reliable and affordable method of creating genetically modified rats provides huge advantages even to small, resource-limited laboratories engaged in biomedical research. Compared to mice, rats are larger and have more developed intelligence and complex behavioral skills. In many cases, they are more suitable for conducting biochemical, pharmacological and physiological studies.
One of the key approaches of the new method is a technique developed by the authors five years ago to prevent the differentiation of sperm progenitor cells into mature germ cells. Researchers have learned how to cultivate lines in the laboratory and genetically modify such cells. After that, they created cell lines carrying the mutations they needed and implanted them into the seminal glands of sterile male rats. As a result, genetically modified spermatozoa were produced in the body of animals, fertilization with the help of which allowed to obtain offspring with certain mutations.
The second secret of success was the method of initiation of mutations in the specified regions of mammalian DNA developed by colleagues from the Max Delbruck Center for Molecular Medicine in Berlin. This method is based on the use of transposons – DNA segments that, when introduced into the genome, begin to move chaotically, creating mutations along the entire trajectory of their movement.
German researchers have learned to clearly control the location and nature of mutations created by a transposon in a particular genome. For example, a transposon can be programmed to create mutations exclusively in a region of the genome containing, according to scientists, genes associated with the disease.
In addition to creating animal lines, Dr. Hamra and his colleagues use the transposon mutation method to create libraries of stem cells carrying various mutations. Currently, they store about 100 such cell lines in liquid nitrogen.
Due to the fact that the seminal glands of one rat can provide sperm production from thousands of individual stem cells, as well as due to the high fertility of rats, such libraries open up new economic strategies for high-performance screening of mutagenesis in rats.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on materials from UT Southwestern Medical Center: UT Southwestern researchers use novel sperm stem-cell technique to produce genetically modified rats.
31.05.2010