Xu's lab tried to modify several of the standard transposons used in other organisms to prod them to hop to mammals, but the researchers' efforts were unsuccessful. Then they tried an unusual transposon called piggyBac, discovered a decade ago by University of Notre Dame professor Malcolm J. Fraser, Jr. PiggyBac appears to be evolutionarily distant from other known transposons and has properties that make it unique. "I thought maybe it's so strange it will work," Xu says. And when Fudan graduate student Sheng Ding introduced piggyBac into mouse and human cells, it did work. In one pilot experiment, Ding and fellow researcher Xiaohui Wu, each working only half-time in their Shanghai research laboratory, generated 75 different knockout mouse mutants in just 3 months.

Besides the agility with which piggyBac lodges itself in mammalian genes, one of its most practical properties is that it can carry additional genes within it, without losing its ability to hop. Xu's team inserted a marker gene that encodes a red fluorescent protein into piggyBac. "You just look at the mice in the next generation, and if they're red you know you have your transposon" without the need for further testing, Xu says. Another advantage is that, like a normal gene, the transposon carries just one copy of the transferred gene into the chromosome, in contrast to traditional transgenic methods that result in multiple copies being inserted. "These features make piggyBac a dream tool for mutating genes," Xu says. He predicts that this new technique will become the method of choice for creating mouse knockouts.

Notre Dame's Fraser, who maintains a Web site for disseminating information about piggyBac to the scientific community, appreciates witnessing the fruits of his discovery: "I congratulate [Xu and colleagues] on the thoroughness of their analysis. It's gratifying to have been involved with finding something that other people can use for such great advantage. That's why you get into science."

For his part, Xu intends to continue Fraser's spirit of scientific openness. "We plan to inactivate the majority of the mouse genes in the next 5 years," he says. "We're going to make those mutant mouse strains available to the scientific community, and I believe this will significantly advance science."

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