Mice with a double heterozygous deficiency of Krüppel-like factor-5 (Klf5) and Fli1 genes represent an SSc animal model able to recapitulate all the three main pathological features of the disease in their specific chronological order, i.e., autoimmunity, microvasculopathy, and tissue fibrosis [84]. The gene discussed is FLI1; the disease is systemic sclerosis.