First Author | Castro Dias M | Year | 2019 |
Journal | Sci Rep | Volume | 9 |
Issue | 1 | Pages | 203 |
PubMed ID | 30659216 | Mgi Jnum | J:275432 |
Mgi Id | MGI:6304673 | Doi | 10.1038/s41598-018-36731-3 |
Citation | Castro Dias M, et al. (2019) Claudin-3-deficient C57BL/6J mice display intact brain barriers. Sci Rep 9(1):203 |
abstractText | The tight junction protein claudin-3 has been identified as a transcriptional target of the Wnt/beta-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. |