Weekly Intraperitoneal Injection of Tamoxifen in an Inducible In Vivo Model of Junctional Epidermolysis Bullosa Generates Early and Advanced Disease Phenotypes.

Junctional epidermolysis bullosa caused by loss-of-function variants in genes encoding the skin basement membrane proteins laminin 332, type XVII collagen, or integrin α6β4 affects patients from birth with severe blistering, eventually leading to scarring and early lethality. In this study, we have optimized a previously published junctional epidermolysis bullosa-knockout mouse model with weekly tamoxifen intraperitoneal injections, resulting in a more controllable and severe model. Owing to the titratable dosing, this model now recapitulates both early and advanced stages of the human disease, strengthening its use in therapeutic studies.

Anti-Laminin β4 IgG Drives Tissue Damage in Anti-p200 Pemphigoid and Shows Interactions with Laminin α3 and γ1/2 Chains.

Laminin β4 was recently identified as a structural component of the dermal-epidermal junction and autoantigen of anti-p200 pemphigoid. In this study, we provided further evidence of the pathogenic effect of anti-laminin β4 IgG and identified potential binding partners of laminin β4. We showed that laminin β4 immune complexes led to activation of normal leukocytes and dose-dependent ROS release.

Laminin β4 is a constituent of the cutaneous basement membrane zone and additional autoantigen of anti-p200 pemphigoid.

Background: Anti-p200 pemphigoid is a subepidermal autoimmune blistering disease (AIBD) characterized by autoantibodies against a 200 kDa protein. Laminin γ1 has been described as target antigen in 70% to 90% of patients. No diagnostic assay is widely available for anti-p200 pemphigoid, which might be due to the unclear pathogenic relevance of anti-laminin γ1 autoantibodies.

Laminin 332 Is Indispensable for Homeostatic Epidermal Differentiation Programs.

The skin epidermis is attached to the underlying dermis by a laminin 332 (Lm332)-rich basement membrane. Consequently, loss of Lm332 leads to the severe blistering disorder epidermolysis bullosa junctionalis in humans and animals. Owing to the indispensable role of Lm332 in keratinocyte adhesion in vivo, the severity of the disease has limited research into other functions of the protein.

Laminins and interaction partners in the architecture of the basement membrane at the dermal-epidermal junction.

The basement membrane at the dermal-epidermal junction keeps the epidermis attached to the dermis. This anatomical barrier is made up of four categories of extracellular matrix proteins: collagen IV, laminin, nidogen and perlecan. These proteins are precisely arranged in a well-defined architecture through specific interactions between the structural domains of the individual components.