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000137318 0247_ $$2doi$$a10.1038/jid.2013.416
000137318 0247_ $$2pmid$$apmid:24121403
000137318 0247_ $$2ISSN$$a0022-202X
000137318 0247_ $$2ISSN$$a1523-1747
000137318 037__ $$aDZNE-2020-03640
000137318 041__ $$aEnglish
000137318 082__ $$a610
000137318 1001_ $$0P:(DE-HGF)0$$aBär, Janina$$b0
000137318 245__ $$aSkin fragility and impaired desmosomal adhesion in mice lacking all keratins.
000137318 260__ $$aAmsterdam$$bElsevier$$c2014
000137318 264_1 $$2Crossref$$3print$$bElsevier BV$$c2014-04-01
000137318 3367_ $$2DRIVER$$aarticle
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000137318 520__ $$aKeratins perform major structural and regulatory functions in epithelia. Owing to redundancy, their respective contribution to epidermal integrity, adhesion, and cell junction formation has not been addressed in full. Unexpectedly, the constitutive deletion of type II keratins in mice was embryonic lethal ∼ E9.5 without extensive tissue damage. This prompted us to analyze keratin functions in skin where keratins are best characterized. Here, we compare the mosaic and complete deletion of all type II keratins in mouse skin, with distinct consequences on epidermal integrity, adhesion, and organismal survival. Mosaic knockout (KO) mice survived ∼ 12 days while global KO mice died perinatally because of extensive epidermal damage. Coinciding with absence of keratins, epidermal fragility, inflammation, increased epidermal thickness, and increased proliferation were noted in both strains of mice, accompanied by significantly smaller desmosomes. Decreased desmosome size was due to accumulation of desmosomal proteins in the cytoplasm, causing intercellular adhesion defects resulting in intercellular splits. Mixing different ratios of wild-type and KO keratinocytes revealed that ∼ 60% of keratin-expressing cells were sufficient to maintain epithelial sheets under stress. Our data reveal a major contribution of keratins to the maintenance of desmosomal adhesion and epidermal integrity with relevance for the treatment of epidermolysis bullosa simplex and other keratinopathies.
000137318 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000137318 542__ $$2Crossref$$i2014-04-01$$uhttps://www.elsevier.com/tdm/userlicense/1.0/
000137318 542__ $$2Crossref$$i2015-12-02$$uhttps://www.elsevier.com/open-access/userlicense/1.0/
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000137318 650_7 $$2NLM Chemicals$$aKeratins, Type II
000137318 650_2 $$2MeSH$$aAnimals
000137318 650_2 $$2MeSH$$aCell Adhesion
000137318 650_2 $$2MeSH$$aCell Membrane: metabolism
000137318 650_2 $$2MeSH$$aCytoplasm: metabolism
000137318 650_2 $$2MeSH$$aDesmosomes: metabolism
000137318 650_2 $$2MeSH$$aDisease Models, Animal
000137318 650_2 $$2MeSH$$aEpidermis: metabolism
000137318 650_2 $$2MeSH$$aEpidermolysis Bullosa Simplex: metabolism
000137318 650_2 $$2MeSH$$aEpithelium: metabolism
000137318 650_2 $$2MeSH$$aGene Deletion
000137318 650_2 $$2MeSH$$aGene Expression Regulation, Developmental
000137318 650_2 $$2MeSH$$aKeratinocytes: metabolism
000137318 650_2 $$2MeSH$$aKeratins, Type II: genetics
000137318 650_2 $$2MeSH$$aKeratins, Type II: metabolism
000137318 650_2 $$2MeSH$$aMice
000137318 650_2 $$2MeSH$$aMice, Knockout
000137318 650_2 $$2MeSH$$aMosaicism
000137318 650_2 $$2MeSH$$aPhenotype
000137318 650_2 $$2MeSH$$aSkin: embryology
000137318 650_2 $$2MeSH$$aSkin: pathology
000137318 7001_ $$0P:(DE-HGF)0$$aKumar, Vinod$$b1
000137318 7001_ $$0P:(DE-2719)2810635$$aRoth, Wera$$b2$$udzne
000137318 7001_ $$0P:(DE-HGF)0$$aSchwarz, Nicole$$b3
000137318 7001_ $$0P:(DE-HGF)0$$aRichter, Miriam$$b4
000137318 7001_ $$0P:(DE-HGF)0$$aLeube, Rudolf E$$b5
000137318 7001_ $$0P:(DE-HGF)0$$aMagin, Thomas M$$b6$$eCorresponding author
000137318 77318 $$2Crossref$$3journal-article$$a10.1038/jid.2013.416$$b : Elsevier BV, 2014-04-01$$n4$$p1012-1022$$tJournal of Investigative Dermatology$$v134$$x0022-202X$$y2014
000137318 773__ $$0PERI:(DE-600)2006902-9$$a10.1038/jid.2013.416$$gVol. 134, no. 4, p. 1012 - 1022$$n4$$p1012-1022$$q134:4<1012 - 1022$$tThe journal of investigative dermatology$$v134$$x0022-202X$$y2014
000137318 8564_ $$uhttps://pub.dzne.de/record/137318/files/DZNE-2020-03640_Restricted.pdf
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000137318 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810635$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE
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000137318 9141_ $$y2014
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