Junctional adhesion molecule (JAM)-C deficient C57BL/6 mice develop a severe hydrocephalus

Wyss, Lena; Schäfer, Julia; Liebner, Stefan; Mittelbronn, Michel; Deutsch, Urban; Enzmann, Gaby; Adams, Ralf H.; Aurrand-Lions, Michel; Plate, Karl H.; Imhof, Beat A.; Engelhardt, Britta (2012). Junctional adhesion molecule (JAM)-C deficient C57BL/6 mice develop a severe hydrocephalus. PLoS ONE, 7(9), e45619. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0045619

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Deutsch, Urban; Enzmann, Gaby and Engelhardt, Britta

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:39

Last Modified:

23 Dec 2014 22:48

Publisher DOI:

10.1371/journal.pone.0045619

PubMed ID:

23029139

Web of Science ID:

000311313900163

BORIS DOI:

10.7892/boris.16031

URI:

https://boris.unibe.ch/id/eprint/16031 (FactScience: 223581)

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