Evidence map›Paper›PMID 31511021›Full record

ArticleFluids and barriers of the CNS2019

Claudin-12 is not required for blood-brain barrier tight junction function.

Mariana Castro Dias, Caroline Coisne, Pascale Baden, Gaby Enzmann, Lillian Garrett, Lore Becker, Sabine M Hölter, German Mouse Clinic Consortium, Martin Hrabě de Angelis, Urban Deutsch and 1 more

Open access · goldAbstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 73 citations in OpenAlex.

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  9. Endothelial mitochondria in the blood-brain barrier.Fluids and barriers of the CNS · 2025
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  19. In vivo methods for imaging blood-brain barrier function and dysfunction.European journal of nuclear medicine and molecular imaging · 2023
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Mariana Castro DiasTheodor Kocher Institute, University of Bern, Freiestr. 1, 3012, Bern, Switzerland.
Caroline CoisneTheodor Kocher Institute, University of Bern, Freiestr. 1, 3012, Bern, Switzerland.
Pascale BadenTheodor Kocher Institute, University of Bern, Freiestr. 1, 3012, Bern, Switzerland.
Gaby EnzmannTheodor Kocher Institute, University of Bern, Freiestr. 1, 3012, Bern, Switzerland.
Lillian GarrettGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Center Munich, Neuherberg, Germany.
Lore BeckerGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Center Munich, Neuherberg, Germany.
Sabine M HölterGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Center Munich, Neuherberg, Germany.
German Mouse Clinic Consortium
Martin Hrabě de AngelisGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Center Munich, Neuherberg, Germany.
Urban DeutschTheodor Kocher Institute, University of Bern, Freiestr. 1, 3012, Bern, Switzerland.
Britta EngelhardtTheodor Kocher Institute, University of Bern, Freiestr. 1, 3012, Bern, Switzerland. bengel@tki.unibe.ch.ORCID http://orcid.org/0000-0003-3059-9846
University of Bern · CHHelmholtz Zentrum München · DE

Funding

EU Horizon 2020 BTRain 675619European Union (EU) Seventh Framework Program FP7 JUSTBRAIN 241861European Union (EU) Seventh Framework Program FP7 nEUROinflammation 607962German Federal Ministry of Education and Research to Infrafrontier 01KX1012
6 · The paper itself

Abstract

backgroundThe blood-brain barrier (BBB) ensures central nervous system (CNS) homeostasis by strictly controlling the passage of molecules and solutes from the bloodstream into the CNS. Complex and continuous tight junctions (TJs) between brain endothelial cells block uncontrolled paracellular diffusion of molecules across the BBB, with claudin-5 being its dominant TJs protein. However, claudin-5 deficient mice still display ultrastructurally normal TJs, suggesting the contribution of other claudins or tight-junction associated proteins in establishing BBB junctional complexes. Expression of claudin-12 at the BBB has been reported, however the exact function and subcellular localization of this atypical claudin remains unknown.

methodsWe created claudin-12-lacZ-knock-in C57BL/6J mice to explore expression of claudin-12 and its role in establishing BBB TJs function during health and neuroinflammation. We furthermore performed a broad standardized phenotypic check-up of the mouse mutant.

resultsMaking use of the lacZ reporter allele, we found claudin-12 to be broadly expressed in numerous organs. In the CNS, expression of claudin-12 was detected in many cell types with very low expression in brain endothelium. Claudin-12

conclusionsOur present study thus shows that claudin-12 is not essential in establishing or maintaining BBB TJs integrity. Claudin-12 is rather expressed in cells that typically lack TJs suggesting that claudin-12 plays a role other than forming classical TJs. At the same time, in depth phenotypic screening of clinically relevant organ functions of claudin-12

Indexed as

AnimalsBlood-Brain BarrierClaudinsEncephalomyelitis, Autoimmune, ExperimentalEndothelial CellsFemaleGene Knock-In TechniquesMaleMice, Inbred C57BLMice, TransgenicTight Junctionsclaudin 12 protein, mouseClaudinsBlood–brain barrierClaudin-12Experimental autoimmune encephalomyelitisTight junctions

Identifiers

PMID31511021
PMCPMC6739961
OpenAlexW2972995082

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.