Genetic variants of Adam17 differentially regulate TGFβ signaling to modify vascular pathology in mice and humans

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 21; pp. 7723 - 7728
• Main Authors: Kawasaki, Kyoko, Freimuth, Julia, Meyer, Dominique S., Lee, Marie M., Tochimoto-Okamoto, Akiko, Benzinou, Michael, Clermont, Frederic F., Wu, Gloria, Roy, Ritu, Letteboer, Tom G. W., van Amstel, Johannes Kristian Ploos, Giraud, Sophie, Dupuis-Girod, Sophie, Lesca, Gaeten, Westermann, Cornelius J. J., Coffey, Robert J., Akhurst, Rosemary J.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 27.05.2014; National Acad Sciences
• Subjects: ADAM Proteins - genetics; ADAM Proteins - metabolism; ADAM17 Protein; Alleles; Angiogenesis; Animals; Biological Sciences; Blood Vessels - pathology; Gene expression regulation; Gene Expression Regulation - genetics; Gene Expression Regulation - physiology; Genetic loci; Genetic mutation; Genetic Variation; Hereditary hemorrhagic telangiectasia; Human genetics; Humans; Immunohistochemistry; Luciferases; Medical genetics; Mice; Mice, Inbred C57BL; NIH 3T3 Cells; Signal Transduction - genetics; Signal Transduction - physiology; Smad2 Protein - metabolism; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta1 - genetics

Outcome of TGFβ1 signaling is context dependent and differs between individuals due to germ-line genetic variation. To explore innate genetic variants that determine differential outcome of reduced TGFβ1 signaling, we dissected the modifier locus Tgfbm3 , on mouse chromosome 12. On a NIH/OlaHsd gene...