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 3rd 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.
Highlights
Junctional adhesion molecules C (JAM-C) is a type I transmembrane protein and a member of the immunoglobulin (Ig) superfamily
When backcrossing junctional adhesion molecule (JAM)-C2/2 mice into the C57BL/6 background we found that JAM-C2/2 C57BL/6 mice developed a severe hydrocephalus
JAM-C2/2 mice housed in individually ventilated cages were born at correct Mendelian ratios (25.4% JAM-C2/2; 47.8% JAM-C+/2 and 26.9% wildtype offspring of 67 animals genotyped between P4 and P11) only 50% of the JAM-C2/2 mice survived until weaning at postnatal day 21 and two thirds of those developed a hydrocephalus within the first 4 to 8 weeks after birth (Table 1)
Summary
Junctional adhesion molecules C (JAM-C) (previously referred to as hJAM-3 and mJAM-2) is a type I transmembrane protein and a member of the immunoglobulin (Ig) superfamily. JAM-C was orignially described on vascular and lymphatic endothelial cells, where it localizes to cell-cell contacts [2] and on human T cells [3]. Since expression of human JAM-C has been detected on additional subsets of leukocytes as well as lymphomas and on platelets Expression of JAM-C has been described on a wide range of non-hematopoietic cells including endothelial and epithelial cells [6], fibroblasts [7], smooth muscle cells [8] and spermatids [9]
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