Targeted Disruption of the Lama3 Gene in Adult Mice Is Sufficient to Induce Skin Inflammation and Fibrosis
| Autor: | Sabrina König, Monique Aumailley, Monika Pesch |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Collagen Type VII Dermatitis Inflammation Dermatology Junctional epidermolysis bullosa (medicine) Biochemistry Mice 03 medical and health sciences Dermis Laminin Fibrosis Keratin medicine Animals Molecular Biology Gene Skin Mice Knockout chemistry.chemical_classification integumentary system biology Epidermis (botany) Cell Biology medicine.disease Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure chemistry Immunology biology.protein medicine.symptom |
| Zdroj: | Journal of Investigative Dermatology. 137:332-340 |
| ISSN: | 0022-202X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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