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Claudin-3-deficient C57BL/6J mice display intact brain barriers
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Claudin-3-deficient C57BL/6J mice display intact brain barriers
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Claudin-3-deficient C57BL/6J mice display intact brain barriers
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Journal Article
Claudin-3-deficient C57BL/6J mice display intact brain barriers
2019
Overview
The tight junction protein claudin-3 has been identified as a transcriptional target of the Wnt/β-catenin signaling pathway regulating blood-brain barrier (BBB) maturation. In neurological disorders loss of claudin-3 immunostaining is observed at the compromised BBB and blood-cerebrospinal fluid barrier (BCSFB). Although these observations support a central role of claudin-3 in regulating brain barriers’ tight junction integrity, expression of claudin-3 at the brain barriers has remained a matter of debate. This prompted us to establish claudin-3
−/−
C57BL/6J mice to study the role of claudin-3 in brain barrier integrity in health and neuroinflammation. Bulk and single cell RNA sequencing and direct comparative qRT-PCR analysis of brain microvascular samples from WT and claudin-3
−/−
mice show beyond doubt that brain endothelial cells do not express claudin-3 mRNA. Detection of claudin-3 protein at the BBB
in vivo
and
in vitro
is rather due to junctional reactivity of anti-claudin-3 antibodies to an unknown antigen still detected in claudin-3
−/−
brain endothelium. We confirm expression and junctional localization of claudin-3 at the BCSFB of the choroid plexus. Our study clarifies that claudin-3 is not expressed at the BBB and shows that absence of claudin-3 does not impair brain barrier function during health and neuroinflammation in C57BL/6J mice.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/1
/ 13/106
/ 13/51
/ 14
/ 14/34
/ 14/63
/ 38
/ 64
/ 82
/ 82/80
/ Animals
/ Antigens
/ Blood-Brain Barrier - metabolism
/ Endothelial Cells - metabolism
/ Female
/ Humanities and Social Sciences
/ Male
/ Mice
/ Proteins
/ Science
/ Tight Junction Proteins - genetics
/ Tight Junction Proteins - metabolism
/ Tight Junctions - metabolism
