Mice that lack activity of αvβ6- and αvβ8-integrins reproduce the abnormalities of Tgfb1- and Tgfb3-null mice

• Published in: Journal of cell science Vol. 122; no. 2; pp. 227 - 232
• Main Authors: Aluwihare, Poshala, Mu, Zhenyu, Zhao, Zhicheng, Yu, Dawen, Weinreb, Paul H, Horan, Gerald S, Violette, Shelia M, Munger, John S
• Format: Journal Article
• Language: English
• Published: The Company of Biologists Limited 15.01.2009; Company of Biologists
• Subjects: Short Report
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.035246

The arginine-glycine-aspartate (RGD)-binding integrins αvβ6 and αvβ8 activate latent TGFβ1 and TGFβ3 in vivo, but it is uncertain whether other RGD-binding integrins such as integrins αvβ5 and αvβ3 activate these TGFβ isoforms. To define the combined role of αvβ6- and αvβ8-integrin in TGFβ activation, we analyzed mice lacking function of both integrins by means of gene deletion and/or pharmacologic inhibition. Most Itgb6⁻/⁻;Itgb8⁻/⁻ embryos die at mid-gestation; those that survive develop cleft palate-as observed in Tgfb3⁻/⁻ mice. Itgb8⁻/⁻ mice treated with an anti-αvβ6-integrin antibody develop severe autoimmunity and lack Langerhans cells-similar to Tgfb1-null mice. These results support a model in which TGFβ3-mediated palate fusion and TGFβ1-mediated suppression of autoimmunity and generation of Langerhans cells require integrins αvβ6 and αvβ8 but not other RGD-binding integrins as TGFβ activators.