TY  - JOUR
AU  - Bär, Janina
AU  - Kumar, Vinod
AU  - Roth, Wera
AU  - Schwarz, Nicole
AU  - Richter, Miriam
AU  - Leube, Rudolf E
AU  - Magin, Thomas M
TI  - Skin fragility and impaired desmosomal adhesion in mice lacking all keratins.
JO  - The journal of investigative dermatology
VL  - 134
IS  - 4
SN  - 0022-202X
CY  - Amsterdam
PB  - Elsevier
M1  - DZNE-2020-03640
SP  - 1012-1022
PY  - 2014
AB  - 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
KW  - Animals
KW  - Cell Adhesion
KW  - Cell Membrane: metabolism
KW  - Cytoplasm: metabolism
KW  - Desmosomes: metabolism
KW  - Disease Models, Animal
KW  - Epidermis: metabolism
KW  - Epidermolysis Bullosa Simplex: metabolism
KW  - Epithelium: metabolism
KW  - Gene Deletion
KW  - Gene Expression Regulation, Developmental
KW  - Keratinocytes: metabolism
KW  - Keratins, Type II: genetics
KW  - Keratins, Type II: metabolism
KW  - Mice
KW  - Mice, Knockout
KW  - Mosaicism
KW  - Phenotype
KW  - Skin: embryology
KW  - Skin: pathology
KW  - Keratins, Type II (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24121403
DO  - DOI:10.1038/jid.2013.416
UR  - https://pub.dzne.de/record/137318
ER  -