title: Targeted Disruption of the Lama3 Gene in Adult Mice Is Sufficient to Induce Skin Inflammation and Fibrosis.
abstract: 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.
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Pesch
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: König
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany. Electronic address: aumailley@uni-koeln.de.
authors.forename: Monique
authors.initials: M
authors.lastname: Aumailley
mesh_terms: D000818:Animals; D024143:Collagen Type VII / Q000378:metabolism; D003872:Dermatitis / Q000209:etiology*; D005355:Fibrosis; D007797:Laminin / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000378:metabolism / Q000473:pathology*
chemical_list: D024143:Collagen Type VII; D007797:Laminin; C095567:laminin alpha 3