TY - JOUR
T1 - Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation.
AU - Chidgey, M
AU - Brakebusch, C
AU - Gustafsson, E
AU - Cruchley, A
AU - Hail, C
AU - Kirk, S
AU - Merritt, A
AU - North, A
AU - Tselepis, C
AU - Hewitt, J
AU - Byrne, C
AU - Fassler, R
AU - Garrod, D
N1 - Keywords: Aging; Alopecia; Animals; Antigens, CD; Cadherins; Cell Differentiation; Cell Division; Dermatitis; Desmosomes; Epidermis; Eyelids; Gene Targeting; Immunohistochemistry; Integrin beta4; Keratins; Ki-67 Antigen; Membrane Glycoproteins; Mice; Mice, Transgenic; Phenotype; Protein Isoforms; Recombination, Genetic; Skin Diseases
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
U2 - 10.1083/jcb.200105009
DO - 10.1083/jcb.200105009
M3 - Journal article
C2 - 11714727
SN - 0021-9525
VL - 155
SP - 821
EP - 832
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 5
ER -
