Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation.
Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation.
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DOI：
10.1083/jcb.200105009
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发表时间：
2001-11-26
影响因子：
7.8
通讯作者：
Garrod, D
中科院分区：
文献类型：
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作者：
Chidgey, M;Brakebusch, C;Gustafsson, E;Cruchley, A;Hail, C;Kirk, S;Merritt, A;North, A;Tselepis, C;Hewitt, J;Byrne, C;Fassler, R;Garrod, D
桥粒钙粘蛋白 desmocollin (Dsc)1 在需要强粘附力的上表皮中表达。为了研究其在体内的作用，我们对小鼠进行了基因工程改造，对 Dsc1 基因进行了有针对性的破坏。出生后不久，无效小鼠就表现出片状皮肤和显着的点状表皮屏障缺陷。表皮脆弱，颗粒层棘层松解会产生局部病变，损害皮肤屏障功能。中性粒细胞在病变处积聚并进一步降解组织，导致病变表皮脱落（剥落），但伤口快速愈合可防止形成明显病变。无效表皮过度增殖并过度表达角蛋白 6 和 16，表明分化异常。从 6 周开始，无效小鼠出现类似慢性皮炎的溃疡性病变。我们推测，脆弱的表皮棘层松解后会发生溃疡，因为与新生小鼠相比，环境损害更严重，伤口愈合速度更慢。这种皮炎伴有与椭圆囊和真皮囊肿形成相关的局部脱发，表明毛囊退化。讨论了病变与人类水疱疾病可能的相似之处。这些结果表明 Dsc1 是表皮强粘附和屏障维持所必需的，并有助于表皮分化。
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.