Sigma® Life Science Introduces World's First P53 Knockout Rat

Sigma® Life Science introduces the world’s first p53 ‘knockout’ rat model, an important development that is expected to, due to the rat’s closer physiological and metabolic similarity to humans, significantly improve timelines for carcinogenicity screening and reduce time to market for therapeutics.

The p53 model, being developed through Sigma Advanced Genetic Engineering (SAGE™) Labs, a Sigma® Life Science initiative, offers the potential for faster and more accurate predictions of how anti-cancer therapeutics work in humans and seeks to increase the understanding of this critical gene. Further characterization of this model is expected to lead to a more comprehensive knowledge of how cancers begin and proliferate. Research applications include early Carcinogenicity screening, Chemopreventive and Chemotherapeutic screening, and p53 pathway studies.

“Over the past twelve months, SAGE Labs has been developing novel rat models, in which specific genes associated with defined disease conditions are deactivated or knocked-out, for use in disease research, especially in areas where the existing mouse models poorly mimic human disease,” said Dr. Edward Weinstein, director of SAGE Labs. “The addition of the p53 model extends our offering into oncology research and builds upon our existing portfolio, which targets applications across a number of fields including physiology, endocrinology, neurology and toxicology. Using our propriatary CompoZr™ Zinc Finger Nuclease platform, we are able to develop mouse or rat models without the need for embryonic stem cells. This enables us to create founder animals in about four to five months, which is about a third of the time it would take using a traditional approach.”

p53 is a tumor suppressor protein encoded by the TP53 gene and is one of the most widely studied cancer-related genes. Its role in the regulation and stabilization of cell cycle, thus preventing genome mutation, is observed among a wide variety of multicellular organisms, including humans, rodents, frogs and fish. Homozygous rats deficient in the p53 protein are expected to be prone to spontaneous tumors and will be valuable for in vivo screening of carcinogenicity, as well as studying chemopreventive and therapeutic treatment.

The colony of p53 knockout rats is currently being expanded and it is anticipated that cohorts of homozygous p53 knockout animals will be available to ship beginning in July 2010.