Mota Castro Dias, Mariana; Coisne, Caroline Marie; Lazarevic, Ivana; Baden, Pascale; Hata, Masaki; Iwamoto, Noriko; Francisco, David Miguel Ferreira; Vanlandewijck, Michael; He, Liqun; Baier, Felix Alexander; Keogh-Stroka, Deborah M.; Bruggmann, Rémy; Lyck, Ruth; Enzmann, Gaby; Deutsch, Urban; Betsholtz, Christer; Furuse, Mikio; Tsukita, Shoichiro; Engelhardt, Britta (2019). Claudin-3-deficient C57BL/6J mice display intact brain barriers. Scientific Reports, 9(1), p. 203. Nature Publishing Group 10.1038/s41598-018-36731-3
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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.
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