SirT1 Conditional Knockout Mice

Introduction SirT1 is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase capable of modifying the activity of many transcription factors that have been implicated in the physiology and pathology of multiple organs. Researchers at the University of Washington have developed a strain of SirT1 conditional knockout mice (SirT1co/co mice). By crossing SirT1co/co mice with CMV-Cre transgenic mice, they generated SirT1-deficient mice and uncovered the function of SirT1 in modulation of estrogen and insulin-like growth factor-1
(IGF-1) signals for mammary gland development. The finding demonstrates that inhibiting SirT1 may attenuate the stimulatory effect of estrogen and IGF-1 signals on normal and malignant mammary epithelial cells, and that SirT1co/co mice can be used to validate the effect of SirT1 antagonists on breast cancer prevention and treatment. Technology description The SirT1 gene in SirT1co/co mice can be deleted in a spatial and temporal manner after they are crossed with a proper strain of Cre transgenic mice. The resultant mice can be used to characterize the physiological and pathological function of SirT1 in vivo. The cells derived from the resultant mice can be used to discover, characterize, and validate compounds that can specifically modulate the enzymatic activity of SirT1. SirT1co/co mice are currently housed in a special-pathogen-free facility. Business opportunity Diet and nutrients influence the activity of SirT1, which in turn affects SirT1’s ability in modulation of the activity of FOXOs, NF-κB, p53, PGC-1α, PPARs, and others. These targets, as well as SirT1 itself, have been implicated in metabolic syndromes, Alzheimer’s disease, and breast cancer. It is estimated that about 178,000 persons will be diagnosed with breast cancer and about 40,000 will die from the disease in 2007. Additionally, nearly 4.5 million of Americans are suffering from Alzheimer’s disease whereas the number of persons affected by metabolic syndrome is even higher. In this regard, SirT1 is an ideal target for dietary and therapeutic intervention. SirT1co/co mice could help the discovery of dietary supplements and SirT1 antagonists/agonists, which could attenuate disease processes and promote healthy lifespan. Related Publication(s)
Breast Cancer Res. 2007 Jan 3;9(1):R1 For more information on this technology contact:
Valerie Carricaburu, Ph.D. Licensing Associate, Invention Licensing 206-543-3970

Type of Offer: Licensing

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