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: Lena Wyss, Julia Schäfer, Stefan Liebner, Michel Mittelbronn, Urban Deutsch, Gaby Enzmann, Ralf H Adams, Michel Aurrand-Lions, Karl H Plate, Beat A Imhof, Britta Engelhardt
• Journal: PloS one (PLoS One) Vol. 7 Issue 9 Pg. e45619 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23029139 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Junctional Adhesion Molecule C

Topics

• Animals
• Base Sequence
• DNA Primers
• Fluorescent Antibody Technique
• Hydrocephalus (genetics)
• Junctional Adhesion Molecule C (genetics, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic