title: Junctional adhesion molecule (JAM)-C deficient C57BL/6 mice develop a severe hydrocephalus.
abstract: The 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.
authors.affiliation: Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Lena
authors.initials: L
authors.lastname: Wyss
authors.forename: Julia
authors.initials: J
authors.lastname: Schäfer
authors.forename: Stefan
authors.initials: S
authors.lastname: Liebner
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.forename: Urban
authors.initials: U
authors.lastname: Deutsch
authors.forename: Gaby
authors.initials: G
authors.lastname: Enzmann
authors.forename: Ralf H
authors.initials: RH
authors.lastname: Adams
authors.forename: Michel
authors.initials: M
authors.lastname: Aurrand-Lions
authors.forename: Karl H
authors.initials: KH
authors.lastname: Plate
authors.forename: Beat A
authors.initials: BA
authors.lastname: Imhof
authors.forename: Britta
authors.initials: B
authors.lastname: Engelhardt
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D006849:Hydrocephalus / Q000235:genetics*; D062786:Junctional Adhesion Molecule C / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D017931:DNA Primers; D062786:Junctional Adhesion Molecule C