Animal Models of Scleroderma: Current State and Recent Development

Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by three cardinal features: immunological abnormalities, vasculopathy, and fibrosis of skin and certain internal organs. Although several animal models recapitulating selected aspects of SSc have been reported, the absence of models fulfilling the full clinical picture of SSc has hindered progress in the development and testing of therapy for this disease. In recent years, three new inducible animal models have revealed the critical importance of reactive oxygen species, angiotensin II, and the combination of DNA topoisomerase I immunization and IL-6 induction in fibrosis of SSc. In addition, two genetic animal models have revealed the potential involvement of transcription factors, Fra-2 and Fli1, in the fibrosis and vasculopathy of SSc. These new animal models provide important insights into specific pathological processes of SSc and novel therapeutic targets that may lead to more effective treatment of this incurable disease.