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Claudin-3-deficient C57BL/6J mice display intact brain barriers
Univ Bern, Theodor Kocher Inst, Bern, Switzerland.
Univ Bern, Theodor Kocher Inst, Bern, Switzerland.
Univ Bern, Theodor Kocher Inst, Bern, Switzerland.
Univ Bern, Theodor Kocher Inst, Bern, Switzerland.
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 203Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2019. Vol. 9, article id 203
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-375813DOI: 10.1038/s41598-018-36731-3ISI: 000456008900001PubMedID: 30659216OAI: oai:DiVA.org:uu-375813DiVA, id: diva2:1285740
Funder
EU, FP7, Seventh Framework Programme, 241861EU, FP7, Seventh Framework Programme, 607962EU, Horizon 2020, 675619 BtRAIN
Note

Correction in: SCIENTIFIC REPORTS, Volume: 9, Article Number: 10702, DOI: 10.1038/s41598-019-43511-0

Available from: 2019-02-05 Created: 2019-02-05 Last updated: 2019-08-16Bibliographically approved

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