ST. LOUIS, April 19, 2012 /PRNewswire/ -- Sigma-Aldrich® Corporation (Nasdaq: SIAL) today announced that Sigma Advanced Genetic Engineering (SAGE) Labs, an initiative of Sigma® Life Science, extended CompoZr® Zinc Finger Nuclease (ZFN) technology to achieve the first tissue-specific conditional knockout of an endogenous gene in rats. For two decades this approach for generating sophisticated disease models could be performed only in mice. Rats, however, are preferred by drug discovery and basic researchers because the animal's physiology, neurobiology and other features are more predictive of human conditions. Rats engineered to contain tissue-specific conditional gene knockouts are available exclusively through the SAGEspeed™ Custom Model Development Service. Details are available at www.sageresearchmodels.com/conditional-KO.
Conventional gene knockout eliminates a gene throughout an entire animal. In contrast, conditional gene knockout can eliminate a gene solely in the relevant tissue or organ, leading to a more accurate understanding of the gene's function. Conditional gene knockout can also knock out genes at certain points in development, enabling studies of genes whose absence in embryos is lethal, but whose loss of function in adulthood is critical to investigate for many human diseases.
"Almost 89% of drug candidates fail to achieve approval," said Edward Weinstein, Director of SAGE Labs. "Basic and drug discovery researchers need access to more predictive animal models whose physiology, biology, and genetics more closely reflect specific human conditions. SAGE Labs is applying ZFN technology to achieve previously impossible genetic manipulations, such as tissue-specific gene deletion in rats."
Using the conditional knockout methodology, scientists at SAGE Labs have generated a pair of rat lines in which two important neuronal genes, Crhr1 and Grin1, were removed in specific neuronal populations. Crhr1 and Grin1 have been implicated as playing a role in depression and schizophrenia, respectively. The rat lines were developed through the SAGEspeed model creation process, which uses Sigma's CompoZr ZFN technology to create sophisticated genetic modifications in rats, mice, rabbits, and other organisms. CompoZr ZFN technology is the first to enable highly efficient, targeted editing of the genome of any species.
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