TY - JOUR
T1 - Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves
AU - Colom, Bartomeu
AU - Poitelon, Yannick
AU - Huang, Wenlong
AU - Woodfin, Abigail
AU - Averill, Sharon
AU - Del Carro, Ubaldo
AU - Zambroni, Desirée
AU - Brain, Susan D.
AU - Perretti, Mauro
AU - Ahluwalia, Amrita
AU - Priestley, John V.
AU - Chavakis, Triantafyllos
AU - Imhof, Beat A.
AU - Feltri, M. Laura
AU - Nourshargh, Sussan
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
KW - Adhesion molecules
KW - Peripheral nerves
KW - Tight junctions
UR - http://www.scopus.com/inward/record.url?scp=84863229734&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863229734&partnerID=8YFLogxK
U2 - 10.1096/fj.11-196220
DO - 10.1096/fj.11-196220
M3 - Article
C2 - 22090315
AN - SCOPUS:84863229734
VL - 26
SP - 1064
EP - 1076
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 3
ER -