Studying Mutant Mice through Mutant Non-Gene DNA

Diseases can result from a mutation of genes (coding segments of DNA that comprise only about 2.5 percent of the entirety of human DNA), and often, mutations of non-gene DNA lead to illness as well. Researchers at the University of Utah recently published a report in the journal Nature Genetics, outlining a faster and more cost-effective method for mutating long stretches of such DNA.

Mario Capecchi, a professor and the co-chair of Human Genetics at the University of Utah and an investigator for the Howard Hughes Medical Institute (HHMI), leads geneticists at the University of Utah in this endeavour. "Diseases are known to occur as a consequence of deleting non-gene DNA sequences, and this new method allows us to evaluate what these sequences do," he says.

Mice are frequently used in studies of human disease and thus, it is beneficial to understand the function of every piece of DNA in the mouse genome. "The best way to know the function of the genetic blueprint is by removing part of the DNA and seeing what goes wrong," says Sen Wu, a postdoctoral fellow in human genetics at the University of Utah and HHMI. Thus, the new technique is especially useful for manipulating the mouse genome and extrapolating the results to the human genome.

With this new technique, certain genes can be easily disabled in the mice genome with significant savings in time and money. Currently, it costs about $10,000 to genetically engineer a mouse with a disabled gene, but the new technique could lower the price to just $200.

To carry this out, Capecchi's team utilized short pieces of DNA called loxP. The loxP is then inserted into the same chromosome on two different mice, but in different positions. The mice are then bred and the resulting offspring carries the loxP DNA at two sites on the same chromosome. The selected chromosome also carries a specific gene, called Cre, which produces a protein that cuts the DNA wherever loxP is found, effectively removing the target DNA from the genome.

According to Capecchi, this new technique could greatly speed up efforts to create 900 new lines of mutant mice by 2010, an accomplishment that "will be extremely useful for the study of human disease", says the National Institutes of Health.

- Written by Andrew Wang.

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