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New technique could alter field of mouse genetics

Howard Hughes Medical Institute researchers have harnessed a mobile gene from the cabbage looper moth and modified it for routine use in mice and other vertebrates. If the new tool works as they expect, it will speed understanding of genes involved in human biology and disease and accelerate the search for effective new therapies.

The researchers report their study in the August 12, 2005, issue of the journal Cell. Certain genes or genetic elements, called transposons, can hop from one place to another in the genomes of various organisms. In people, this genetic shuffling ensures that the immune system can generate a huge assortment of protective antibodies. Bacteria use the mechanism to swap antibiotic-resistance genes among themselves. And scientists have "borrowed" and adapted the same handy technique to insert genes and mutate genes in fruit flies and simpler organisms to learn the function of individual genes.

"We know how many genes are in the genome, but that does not tell us how they carry out their jobs," said senior author Tian Xu, a Howard Hughes Medical Institute (HHMI) investigator at Yale University School of Medicine. "We have found a way to systematically inactivate genes in the mouse genome so we understand the functions of these genes."

With a large inventory of genome sequences in hand, over the last few years many scientists have shifted their attention to determining the function of all of those genes. The strategy is as systematic as the genome sequencing projects -- mutate each gene, observe the consequences, and investigate the molecular mechanisms. In the past two decades, only about 3,000 of the estimated 25,000 genes shared by mice and humans have been analyzed in detail, Xu said. A reliable gene-transposing tool could make that job much easier and quicker.

Xu and his colleagues at Fudan University in Shanghai, China, began their studies with a transposon called piggyBac. With the help of a partner enzyme, pi
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Source:Howard Hughes Medical Institute


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