Caveolin 1 (Cav1) is the gene product of the Cav1 locus. Cav1 is a phosphoprotein with a structural role in the formation of caveolae, organelles with a variety of assigned functions. Cav1 is involved in multiple signal transduction pathways, and is believed to be a tumor suppressor, as well as an angiogenesis inhibitor. Caveolae are involved in mechanical sensing, buffering of membrane tension in cells under stretch, as well as in inflammation and permeability. Loss of Cav1 results in severe dyslipidemia and a cardiovascular phenotype with dilative cardiomyopathy and pulmonary hypertension. In addition, loss of Cav1 protein results in a type II diabetes syndrome with hyperglyceridemia, hyperinsulinemia and decreased tolerance to glucose.
Using heterologous recombination, Dartmouth researchers have now generated a Caveolin 1 (Cav1) knock-in mouse. The knock-in construct used in the generation of the transgenic mouse is composed of nucleic acids encoding Cav1 fused in-frame with nucleic acids encoding the reporter protein GFP. The knock-in construct further included the marker expression cassette encoding the neomycin resistant gene flanked by loxP recombinase target sites, wherein the neomycin expression cassette disrupts the Cav1 locus of the knock-in construct, thereby resulting in a Cav1 null allele. Using the transgenic mouse, Cav1-GFP expression can be controlled in a time- and/or tissue- specific manner by crossing the Cav1 knock-in mouse with a transgenic mouse expressing a recombinase, such as Cre recombinase, the expression of which is under the control of a time- and/or tissue-specific promoter. These mice are of use in in vivo studies of vascular permeability and formation of fat (adipose) tissue, and in analyzing cardiovascular functions and diseases where caveolae have been implicated, e.g., atherosclerosis and tumor angiogenesis.
This technology is claimed in the published PCT application No. PCT/US2010/035706. We are seeking an industrial partner interested in its commercialization. (Ref: J509)
Last Updated: 7/24/12