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@ARTICLE{Br:137318,
author = {Bär, Janina and Kumar, Vinod and Roth, Wera and Schwarz,
Nicole and Richter, Miriam and Leube, Rudolf E and Magin,
Thomas M},
title = {{S}kin fragility and impaired desmosomal adhesion in mice
lacking all keratins.},
journal = {The journal of investigative dermatology},
volume = {134},
number = {4},
issn = {0022-202X},
address = {Amsterdam},
publisher = {Elsevier},
reportid = {DZNE-2020-03640},
pages = {1012-1022},
year = {2014},
abstract = {Keratins 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.},
keywords = {Animals / Cell Adhesion / Cell Membrane: metabolism /
Cytoplasm: metabolism / Desmosomes: metabolism / Disease
Models, Animal / Epidermis: metabolism / Epidermolysis
Bullosa Simplex: metabolism / Epithelium: metabolism / Gene
Deletion / Gene Expression Regulation, Developmental /
Keratinocytes: metabolism / Keratins, Type II: genetics /
Keratins, Type II: metabolism / Mice / Mice, Knockout /
Mosaicism / Phenotype / Skin: embryology / Skin: pathology /
Keratins, Type II (NLM Chemicals)},
cin = {AG Fava 1},
ddc = {610},
cid = {I:(DE-2719)1013016},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:24121403},
doi = {10.1038/jid.2013.416},
url = {https://pub.dzne.de/record/137318},
}