Wyss, LenaLenaWyssSchäfer, JuliaJuliaSchäferLiebner, StefanStefanLiebnerMittelbronn, MichelMichelMittelbronnDeutsch, UrbanUrbanDeutschEnzmann, GabyGabyEnzmannAdams, Ralf H.Ralf H.AdamsAurrand-Lions, MichelMichelAurrand-LionsPlate, Karl H.Karl H.PlateImhof, Beat A.Beat A.ImhofEngelhardt, BrittaBrittaEngelhardt0000-0003-3059-98462024-10-132024-10-132012https://boris-portal.unibe.ch/handle/20.500.12422/90069The junctional adhesion molecule (JAM)-C is a widely expressed adhesion molecule regulating cell adhesion, cell polarity and inflammation. JAM-C expression and function in the central nervous system (CNS) has been poorly characterized to date. Here we show that JAM-C(-/-) mice backcrossed onto the C57BL/6 genetic background developed a severe hydrocephalus. An in depth immunohistochemical study revealed specific immunostaining for JAM-C in vascular endothelial cells in the CNS parenchyma, the meninges and in the choroid plexus of healthy C57BL/6 mice. Additional JAM-C immunostaining was detected on ependymal cells lining the ventricles and on choroid plexus epithelial cells. Despite the presence of hemorrhages in the brains of JAM-C(-/-) mice, our study demonstrates that development of the hydrocephalus was not due to a vascular function of JAM-C as endothelial re-expression of JAM-C failed to rescue the hydrocephalus phenotype of JAM-C(-/-) C57BL/6 mice. Evaluation of cerebrospinal fluid (CSF) circulation within the ventricular system of JAM-C(-/-) mice excluded occlusion of the cerebral aqueduct as the cause of hydrocephalus development but showed the acquisition of a block or reduction of CSF drainage from the lateral to the 3(rd) ventricle in JAM-C(-/-) C57BL/6 mice. Taken together, our study suggests that JAM-C(-/-) C57BL/6 mice model the important role for JAM-C in brain development and CSF homeostasis as recently observed in humans with a loss-of-function mutation in JAM-C.enarticle10.7892/boris.160312302913900031131390016310.1371/journal.pone.0045619