Cancer gene scores a mouse knockout.

Small, infertile, beset with neurological problems, and prone to deadly cancer within their first few months of life, the mice in Anthony Wynshaw- Boris' laboratory at the National Center for Human Genome Research in Bethesda, Md., are an unenviable lot. When subjected to ionizing radiation, the mice die from cancer much more readily than normal mice. The sad state of these rodents stems from their inability to synthesize the protein encoded by a gene called ATM.

Children who have mutations in both their copies of the human version of this gene suffer from a fatal condition called ataxia-telangiectasia, marked in its early stages by slurred speech and involuntary movements. Those afflicted also run a higher than normal risk of cancer.

The knockout mice, so called because their ATM genes have been knocked out by scientists, suffer problems remarkably similar to those of humans with ataxia-telangiectasia, note Wynshaw-Boris and his colleagues in the July 12 Cell. As a result, the researchers expect that studying the mutant mice will help them understand the function of the protein encoded by the ATM gene.

Previous studies suggest it plays a role in repairing damaged DNA.

"The fact that we have a good model will also allow us to test a lot of things that might [alleviate] ataxia-telangiectasia. We can try more speculative therapies on a mouse than we would dare try on humans," says Wynshaw-Boris.

Some research has suggested that carriers of ataxia-telangiectasia, who have one mutant copy and one normal copy of the ATM gene, may be more vulnerable to cancer, particularly breast cancer. The investigators are therefore looking also at mice with only one mutant copy of the ATM gene. "If there's an increased risk of cancer, we would hope to see it in our mice," says Wynshaw-Boris. Though none of these mice have developed tumors so far, investigators caution that they have followed the animals for only a few months.