Schwann cell‐specific JAM‐C‐deficient mice reveal novel expression and functions for JAM‐C in peripheral nerves

• Published in: The FASEB journal Vol. 26; no. 3; pp. 1064 - 1076
• Main Authors: Colom, Bartomeu, Poitelon, Yannick, Huang, Wenlong, Woodfin, Abigail, Averill, Sharon, Carro, Ubaldo Del, Zambroni, Desirée, Brain, Susan D., Perretti, Mauro, Ahluwalia, Amrita, Priestley, John V., Chavakis, Triantafyllos, Imhof, Beat A., Feltri, M. Laura, Nourshargh, Sussan
• Format: Journal Article
• Language: English
• Published: Bethesda, MD, USA Federation of American Societies for Experimental Biology 01.03.2012
• Subjects: adhesion molecules; Animals; Blotting, Western; Calcitonin Gene-Related Peptide - metabolism; Cell Adhesion Molecules - deficiency; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - physiology; Endothelial Cells - metabolism; Epithelial Cells - metabolism; Female; Immunoglobulins - deficiency; Immunoglobulins - genetics; Immunoglobulins - physiology; Immunohistochemistry; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Microscopy, Confocal; Microscopy, Electron; Motor Neurons - metabolism; Muscle, Skeletal - cytology; Muscle, Skeletal - injuries; Muscle, Skeletal - metabolism; Nerve Fibers - metabolism; peripheral nerves; Peripheral Nerves - cytology; Peripheral Nerves - metabolism; Peripheral Nerves - physiology; Reflex - physiology; Schwann Cells - metabolism; Sciatic Nerve - metabolism; Sciatic Nerve - physiology; Sciatic Nerve - ultrastructure; Sensory Receptor Cells - metabolism; tight junctions
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.11-196220

Junctional adhesion molecule‐C (JAM‐C) is an adhesion molecule expressed at junctions between adjacent endothelial and epithelial cells and implicated in multiple inflammatory and vascular responses. In addition, we recently reported on the expression of JAM‐C in Schwann cells (SCs) and its importance for the integrity and function of peripheral nerves. To investigate the role of JAM‐C in neuronal functions further, mice with a specific deletion of JAM‐C in SCs (JAM‐C SC KO) were generated. Compared to wild‐type (WT) controls, JAM‐C SC KO mice showed electrophysiological defects, muscular weakness, and hypersensitivity to mechanical stimuli. In addressing the underlying cause of these defects, nerves from JAM‐C SC KO mice were found to have morphological defects in the paranodal region, exhibiting increased nodal length as compared to WTs. The study also reports on previously undetected expressions of JAM‐C, namely on perineural cells, and in line with nociception defects of the JAM‐C SC KO animals, on finely myelinated sensory nerve fibers. Collectively, the generation and characterization of JAM‐C SC KO mice has provided unequivocal evidence for the involvement of SC JAM‐C in the fine organization of peripheral nerves and in modulating multiple neuronal responses.—Colom, B., Poitelon, Y., Huang, W., Woodfin, A., Averill, S., Del Carro, U., Zambroni, D., Brain, S. D., Perretti, M., Ahluwalia, A., Priestley, J. V., Chavakis, T., Imhof, B. A., Feltri, M. L., Nourshargh, S. Schwann cell‐specific JAM‐C‐deficient mice reveal novel expression and functions for JAM‐C in peripheral nerves. FASEB J. 26, 1064–1076 (2012). www.fasebj.org