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New technique could alter field of mouse genetics

other genes effectively. Inserted into mouse embryos, the transposon and its cargo was inherited through five generations. PiggyBac can also be removed from its place in the family tree by breeding a mouse with another that carries the enzyme necessary to excise the jumping gene.

"We do not know why the P element did not work in mammalian organisms, and we do not know why this particular one works," Xu said, "but this system is a dream tool for geneticists working with vertebrates and mammals."

PiggyBac inserts randomly into the genome, with a clear preference for genes. This bodes well for its use in mutating genes and for identifying unrecognized genes in places of the genome that have been especially difficult to sequence. Furthermore, the markers it carries make it easy to find. In Xu's lab, the jumping gene carried red fluorescent protein and an enzyme that changes the coat color of a white mouse to grey or black. The transposon acts as a genetic beacon, so researchers can easily track its location without having to sequence the entire genome, as can happen with the chemical mutagen technique.

In three months, the two graduate students who led the project, generated knockout mice for each of 75 different genes. Xu, Min Han, an HHMI investigator at the University of Colorado, Boulder, and Yuan Zhuang of Duke University, and their colleagues at Fudan University are in the process of scaling up piggyBac for the Mouse Functional Genome Project, which is aiming to mutate the majority of mouse genes at a state-of-the-art research facility in China. Xu expects the technique to be particularly useful for animal models of genetically complex diseases, such as diabetes, where many genes contribute to the disease process.


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Source:Howard Hughes Medical Institute


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