Bolon I Zhou HM Charron Y Wohlwend A Vassalli JD 2004 Increased expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) is associated with different pathological conditions. Both uPAR-mediated signaling and plasmin-catalyzed extracellular proteolysis may contribute to pathogenesis. To evaluate the involvement of plasminogen in such circumstances, we have taken advantage of transgenic mouse models in which overexpression of uPA and/or uPAR in enamel epithelium, basal epidermis, and hair follicles leads to a pathological phenotype; uPA transgenic mice have chalky-white incisors and, when uPAR is co-expressed, develop extensive alopecia, epidermal thickening, and subepidermal blisters. We report here that when these transgenic mice were backcrossed into a plasminogen-deficient (Plg-/-) background, the dental and skin phenotypes appeared completely normal. Heterozygous Plg+/- transgenic mice exhibited a haplo-insufficiency, with an intermediate or normal phenotype. These results do not argue in favor of a role for uPAR-mediated signaling in our experimental model; rather, they demonstrate an essential, dose-dependent, requirement for plasminogen in uPA-mediated tissue alterations. They also support the hypothesis that plasminogen could play a part in certain skin diseases. application/pdf https://sonar.ch/global/documents/5386 eng info:eu-repo/semantics/altIdentifier/doi/10.1016/S0002-9440(10)63786-8 info:eu-repo/semantics/altIdentifier/pmid/15161662 info:eu-repo/semantics/openAccess The American journal of pathology. - 2004 Animals Crosses, Genetic Dental Enamel Dental Enamel Hypoplasia Gene Expression Regulation Incisor Mice Mice, Inbred C57BL Mice, Inbred CBA Mice, Transgenic Phenotype Plasminogen Receptors, Cell Surface Receptors, Urokinase Plasminogen Activator Tooth Abnormalities Urokinase-Type Plasminogen Activator Plasminogen mediates the pathological effects of urokinase-type plasminogen activator overexpression. http://purl.org/coar/resource_type/c_6501