UROKINASE-TYPE PLASMINOGEN ACTIVATOR-DEFICIENT MICE ARE PREDISPOSED TO STAPHYLOCOCCAL BOTRYOMYCOSIS, PLEURITIS, AND EFFACEMENT OF LYMPHOID FOLLICLES

Urokinase-type plasminogen activator (uPA) is thought to be an importa nt mediator in the proteolytic degradation of extracellular matrix com ponents observed in a wide variety of normal physiological and patholo gical conditions. However, the phenotype of a recently developed strai n of urokinase-deficient (uPA-/-) mice appears to be normal when maint ained under ideal nonstressful conditions. We report an outbreak of bo tryomycosis, an unusual staphylococcal infection, in a colony of uPA-d eficient mice. A detailed histological examination of these uPA-defici ent animals also revealed a variety of previously unreported phenotypi c abnormalities such as pleuritis and the effacement of lymphoid folli cles in the regional lymph nodes and spleen. Additional phenotypic abn ormalities such as dystrophic calcifications and rectal prolapse were also observed in the uPA-deficient population. These abnormalities wer e also noted in ostensibly healthy uPA-deficient animals. Botryomycosi s did not affect a colony of wild-type (uPA+/+) animals maintained con currently under identical conditions in the same room. The peculiar pr edisposition of the uPA-deficient animals to this rare bacterial infec tion and the development of phenotypic abnormalities associated with t he targeted disruption the uPA gene suggests that uPA contributes sign ificantly to the cutaneous microenvironment and is additional evidence of the extensive involvement of the plasminogen activators in mammali an physiology.