( ur so that cancer develops. “If w...)Mutating the entire genome

“If we now improve that 10,000-fold, the pool of cells [with translocated chromosomes] may be large enough to create a mouse that develops the cancer,” so the new method makes it easier to breed mice with human cancers, Capecchi says.

‘Jumping Genes’ Help Make More Mutant DNA

Wu and Capecchi improved their new method by using it in combination with a “transposon” or so-called “jumping gene” named piggyBac, which comes from a moth. They used piggyBac to insert pieces of loxP DNA randomly into numerous spots on the mouse genome. So scientists easily can breed multiple generations of mice with loxP surrounding various large stretches of DNA.

Then the first part of the new method is used: The mice are bred with mice that carry the Cre gene so any large stretch of DNA that is located between two short pieces of loxP DNA can be mutated.

Because the whole mouse genome has been sequenced – the order and location of base pairs determined in detail – scientists can identify locations in individual mice where the jumping genes have carried pieces of loxP DNA. Then, they can select a mouse with loxP on both sides of the large piece of DNA they want to mutate and study.

If the jumping gene carrying loxP hops into the middle of a gene, then the gene will be mutated. So while the method began as a way to delete large stretches of non-gene DNA, it has the bonus of also being able to disable genes more easily and inexpensively than existing knockout techniques, Wu says.

In their study, Wu and Capecchi demonstrated that by using a jumping gene to mutate a mouse gene involved in bone formation, resulting in mutant mice with abnormally short limbs and tail (see photo with this news release).
'"/>

Source:University of Utah Health Sciences Center