Targeted Disruption of the Lama3 Gene in Adult Mice Is Sufficient to Induce Skin Inflammation and Fibrosis

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• 作者：Monika Pesch¹ ; Sabrina Kö ; nig¹ ; Monique Aumailley¹ ; ^{aumailley@uni-koeln.de}
• 关键词：bp ; base pair ; Ctr ; tamoxifen-treated heterozygous Lama3wt/flox/K14-CreERT ; eKO ; tamoxifen-treated homozygous Lama3flox/flox/K14-CreERT ; IFE ; interfollicular epidermis ; JEB ; junctional epidermolysis bullosa ; K ; keratin ; LM ; laminin
• 刊名：Journal of Investigative Dermatology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：137
• 期：2
• 页码：332-340
• 全文大小：3832 K
• 卷排序：137

文摘

Genetic, clinical, and biochemical studies have shown that integrity of the dermal-epidermal junction requires a particular subset of laminins, that is, those containing the α3 chain encoded by the Lama3 gene. Inherited mutations in the human gene or introduction of constitutive mutations in the mouse gene prevent expression of these laminins, causing junctional epidermolysis bullosa, a very severe, often lethal disorder characterized by detachment of the epidermis from the dermis. This has precluded in vivo functional analysis of α3 chain-containing laminins, and it is still unknown whether and how they contribute to adult skin homeostasis. To address this question, we have disrupted the Lama3 gene in basal keratinocytes of adult mice. This led to the gradual disappearance of α3 chain-containing laminins along the dermal-epidermal junction and formation of subepidermal blisters like in congenital junctional epidermis bullosa. The mice lose their nails and have bullae and erosions on the footpads. Because the blistering is restricted to the interfollicular epidermis, the animals do not lose the epidermis and are viable. There is abundant and scattered deposition of collagen VII on the dermal side of the blisters, inflammation, and development of skin fibrosis with extensive accumulation of interstitial and microfibrillar collagens.