Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation
Autor: | A. T. Cruchley, Carolyn Byrne, Chris Tselepis, Jane E. Hewitt, Alison J. North, Sarah E. Kirk, David R. Garrod, Cord Brakebusch, Martyn A.J. Chidgey, Chris Hail, Reinhard Fässler, Erika Gustafsson, Anita J. Merritt |
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Rok vydání: | 2001 |
Předmět: |
Aging
Pathology medicine.medical_specialty Dermatitis Mice Transgenic Biology Skin Diseases Article Mice 03 medical and health sciences 0302 clinical medicine Antigens CD Desmosome medicine Animals Protein Isoforms 030304 developmental biology Desmocollins Recombination Genetic 0303 health sciences DSC3 Membrane Glycoproteins desmosome desmocollin epidermis epidermal barrier null mutation integumentary system Epidermis (botany) Cadherin Acantholysis Integrin beta4 Eyelids Alopecia Cell Differentiation Desmosomes Cell Biology Cadherins Hair follicle medicine.disease Immunohistochemistry Ki-67 Antigen Phenotype medicine.anatomical_structure 030220 oncology & carcinogenesis Gene Targeting Immunology Keratins Desmocollin Epidermis Wound healing Cell Division |
Zdroj: | The Journal of Cell Biology |
ISSN: | 1540-8140 0021-9525 |
Popis: | The desmosomal cadherin desmocollin (Dsc)1 is expressed in upper epidermis where strong adhesion is required. To investigate its role in vivo, we have genetically engineered mice with a targeted disruption in the Dsc1 gene. Soon after birth, null mice exhibit flaky skin and a striking punctate epidermal barrier defect. The epidermis is fragile, and acantholysis in the granular layer generates localized lesions, compromising skin barrier function. Neutrophils accumulate in the lesions and further degrade the tissue, causing sloughing (flaking) of lesional epidermis, but rapid wound healing prevents the formation of overt lesions. Null epidermis is hyperproliferative and overexpresses keratins 6 and 16, indicating abnormal differentiation. From 6 wk, null mice develop ulcerating lesions resembling chronic dermatitis. We speculate that ulceration occurs after acantholysis in the fragile epidermis because environmental insults are more stringent and wound healing is less rapid than in neonatal mice. This dermatitis is accompanied by localized hair loss associated with formation of utriculi and dermal cysts, denoting hair follicle degeneration. Possible resemblance of the lesions to human blistering diseases is discussed. These results show that Dsc1 is required for strong adhesion and barrier maintenance in epidermis and contributes to epidermal differentiation. |
Databáze: | OpenAIRE |
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