Sigma® Life Science Announces Gene Knockout Rat Models for Cardiovascular, Diabetes and Atherosclerosis Research

ST. LOUIS, Dec. 7, 2011 /PRNewswire/ -- Sigma-Aldrich® Corporation (Nasdaq: SIAL) today announced that Sigma Advanced Genetic Engineering (SAGE) Labs, an initiative of Sigma Life Science, has made available three genetically modified rat models that exhibit features key to studying conditions such as obesity, diabetes, atherosclerosis, high cholesterol, hypertension and familial hypercholesterolemia. Details on the models are available at

"Leptin, LDL receptor and ApoE gene knockout rats display phenotypes, physiology and metabolism sorely needed in studies of human cardiovascular diseases and diabetes, without requiring special, costly high-fat diets," explained Edward Weinstein, Director of SAGE Labs.

Leptin is a protein that regulates energy intake and expenditure. Loss of functional Leptin causes uncontrolled appetite, leading to severe obesity and abnormal metabolism. The Leptin knockout rats (KiloRat) weigh almost double age-matched rats and have elevated serum cholesterol and triglyceride levels. The KiloRats also show signs of insulin resistance, a critical feature for diabetes research.

The low density lipoprotein (LDL) receptor knockout rats, which lack the receptor essential to preventing accumulation of LDL-cholesterol in the blood, have blood cholesterol levels 4-8 times higher than age-matched rats on low or high-fat diets. Elevated blood LDL is directly involved with the development of atherosclerosis, the process responsible for the majority of cardiovascular diseases.

Apolipoprotein E (ApoE) is a protein that is essential for normal processing of triglyceride-rich lipoprotein constituents. The disruption of ApoE, results in errant movement of lipoproteins, fat-soluble vitamins, and cholesterol into the lymph system, and then into the blood. The ApoE knockout rats demonstrate a 4.5 fold increase in total serum cholesterol concentration at 10 weeks relative to the age-matched rats with normal diet. In addition to utility for studies of cardiovascular disease and diabetes, ApoE has recently been implicated in Alzheimer's disease, cognitive degeneration, immune system regulation and nerve injury repair.

Animal models with knockouts of LDL receptor or ApoE genes were previously available only in mice. "Rats are widely recognized as more indicative models of human cardiovascular disease, diabetes and atherosclerosis. A rat's heart rate is much closer to a human's and grows much larger, which enables more detailed physiological measurements and procedures, such as more frequent blood testing and insertion of stents," Weinstein explained. "And, critically, drug safety tests are performed in rats downstream. Using the same model organism from discovery to drug development enables much earlier and clearer answers to the key question: will this therapeutic translate into humans?"

Additional gene knockout rat models for cardiovascular disease and diabetes research are expected to be released in early 2012.

Scientists at SAGE Labs created the gene knockout rats through the SAGEspeed model creation process, which uses Sigma's CompoZr® Zinc Finger Nuclease (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. For more information, visit

Cautionary Statement: The foregoing release contains forward-looking statements that can be identified by terminology such as "enables,"  "ideally suited" or similar expressions, or by expressed or implied discussions regarding potential future revenues from products derived therefrom. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that the gene knockout rats will assist the Company to achieve any particular levels of revenue in the future. In particular, management's expectations regarding products associated with the gene knockout rats could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; the Company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; the impact that the foregoing factors could have on the values attributed to the Company's assets and liabilities as recorded in its consolidated balance sheet, and other risks and factors referred to in Sigma-Aldrich's current Form 10-K on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Sigma-Aldrich is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Sigma Life Science: Sigma Life Science is a Sigma-Aldrich business that represents the Company's leadership in innovative biological products and services for the global life science market and offers an array of biologically-rich products and reagents that researchers use in scientific investigation. Product areas include biomolecules, genomics and functional genomics, cells and cell-based assays, transgenics, protein assays, stem cell research, epigenetics and custom services/oligonucleotides. Sigma Life Science also provides an extensive range critical bioessentials like biochemicals, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, amino acids and their derivatives, and cell culture media.

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Sigma-Aldrich and Sigma are trademarks of Sigma-Aldrich Co, LLC registered in the US and other countries.  CompoZr is a registered trademark of Sigma-Aldrich Co, LLC. SAGE, KiloRat and SAGEspeed are trademarks of Sigma-Aldrich Co, LLC. Sprague Dawley® is a U.S. registered trademark and trademark of Harlan Laboratories, Inc.

SOURCE Sigma-Aldrich Corporation