World's First p53 Knockout Rat Developed to Improve Carcinogenicity Screening

The world's first p53 "knockout” rat model has been introduced: an important development due to the rat's closer physiologic and metabolic similarity to humans that is expected to improve timelines for carcinogenicity screening considerably and reduce time to market for therapeutics.

The p53 model, being developed through Sigma Life Science, the biologic products and services brand of Sigma-Aldrich's (St. Louis, MO, USA) Advanced Genetic Engineering (SAGE) Labs - a Sigma Life Science initiative, offers the potential for faster and more effective predictions of how anticancer therapeutics work in humans and seeks to increase the understanding of this crucial gene. Additional characterization of this model is expected to lead to a more comprehensive knowledge of how tumors begin and proliferate. Research applications include early carcinogenicity screening, chemopreventive and chemotherapeutic screening, and p53 pathway studies.

"Over the past 12 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,” stated 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 proprietary 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, thereby 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 they 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.

Sigma Life Science provides biologic products and services for the global life science market and an array of biologically rich products and reagents that researchers use in scientific investigation.

SAGE Labs, a Sigma Life Science initiative, is a provider of research models, including knockout rat models, and extensive support services. Using Sigma's proprietary platform technologies, SAGE specializes in genetic manipulation of in vivo systems for specialized R&D applications. SAGE Labs specializes in the development and characterization of unique, next-generation animal research models featuring specific gene deletions, insertions, repressions, and modifications using proprietary CompoZr ZFN (zinc finger nuclease) technology.

Sigma-Aldrich's biochemical and organic chemical products and kits are used in scientific research, including genomic and proteomic research, biotechnology, pharmaceutical development and as key components in pharmaceutical, diagnostic, and other high technology manufacturing.

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