Knockout of Aryl Hydrocarbon Receptor (AhR) and its Binding Partner Aryl Hydrocarbon Receptor Nuclear Translocator (Arnt) each i
Posted Jun 15 2010 5:00pm
Description of Invention: The technology relates to two separate knockout mouse models of related transcription factors that bind each other. The aryl hydrocarbon receptor (AhR) and the aryl hydrocarbon receptor nuclear translocator (Arnt) protein are transcription factors that play an important role in mediating the effects of man-made environmental toxins. They also play a role in mammalian development and physiological homeostasis. Members of the PAS domain/bHLH family of transcription factors, they are obligate dimerization partners with each other and other members of this family, such as hypoxia-inducible factor 1alpha (HIF1alpha). These transcription factors have been shown to be important in a number of specific tissues including ovary, vascular endothelium, keratinocytes, T-cells, and liver.
Available for licensing is a knockout mouse line in which the AhR receptor has been knocked-out, and a mouse line containing a floxed allele of the Arnt gene. The Arnt mouse line can be used to disrupt the Arnt gene in different tissues by breeding the Arnt-floxed mice with transgenic mice in which the Cre recombinase is under the control of tissue-specific promoters. These mice may be used as a research tool for drug development where PAS/bHLH transcription factors are targeted.
Tool for drug studies targeting PAS/bHLH transcription factors
Tool to probe the role of the Arnt protein in a tissue-specific manner
Research Tools -- patent protection is not being pursued for these technologies.
S Tomita, CJ Sinal, SH Yim, and FJ Gonzalez. Conditional disruption of the aryl hydrocarbon receptor nuclear translocator (Arnt) gene leads to loss of target gene induction by the aryl hydrocarbon receptor and hypoxia-inducible factor 1alpha. Mol Endocrinol. 2000 Oct;14(10):1674-1681. [ PubMed abs ]
SH Yim, Y Shah, S Tomita, HD Morris, O Gavrilova, G Lambert, JM Ward, and FJ Gonzalez. Disruption of the Arnt gene in endothelial cells causes hepatic vascular defects and partial embryonic lethality in mice. Hepatology. 2006 Sep;44(3):550-560. [ PubMed abs ]
P Fernandez-Salguero et al. Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor. Science 1995 May 5;268(5211):722-726. [ PubMed abs ]
Licensing Status: This technology is available as a research tool under a Biological Materials License.
Collaborative Research Opportunity: The National Cancer Institute, Laboratory of Metabolism, Center for Cancer Research, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or firstname.lastname@example.org for more information.
Portfolios: Internal Medicine Internal Medicine - Research Materials Animal Model
For Additional Information Please Contact: Steven Standley Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: email@example.com Phone: 301-435-4074 Fax: 301-402-0220