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UT Southwestern researchers use novel sperm stem-cell technique to produce genetically modified rats
Date:5/27/2010

"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 Izsvk and Zoltn 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 librari
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Contact: Amanda Siegfried
amanda.siegfried@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert  

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