
Scientists have deliberately mutated the p53 tumor suppressor gene in rats using embryonic stem cells, according to a paper published today in Nature. Although similar knockout rats have previously been created with another technology, namely zinc finger nucleases, the stem cell-based technique could prove cheaper and more versatile for creating sophisticated animal models of disease.
Earlier this year, I reported how Qi-Long Ying and his colleagues at the University of Southern California in Los Angeles had used homologous recombination to knock out the p53 gene and create 20 chimeric rats. At the time that my story ran in March, however, none of the animals had given birth to p53-deficient pups.
After tinkering with his cell culturing system, Ying repeated the experiment in February. “This time we have a very big chance that we’ll make chimeras, and I think we’ll get germline transmission,” Ying told me at the time.
Long story short: it worked.
Ying’s team is now studying the p53 knockouts to determine how missing the gene affects the rodents’ susceptibility to liver cancer, The Great Beyond reports. The researchers are also working to build other knockout rats including animals lacking a key immune system gene. Again, however, Ying’s team might be playing catch up with others who have turned to zinc finger nucleases. For example, in January a Japanese team generated knockout rats with X-linked severe combined immunodeficiency using the zinc finger technique.
Image: Chang Tong, University of Southern California