In perspective: murine models of scleroderma

An understanding of the complex pathogenesis of systemic sclerosis (SSc) has been slow to emerge, due in large part to the lack of an animal model recapitulating the three cardinal attributes of SSc: autoimmunity, vasculopathy, and fibrosis. Experimental manipulations in inbred murine strains can lead to conditions that mimic SSc fibrosis. Furthermore, genetic engineering has enabled the creation of novel murine strains that spontaneously develop fibrosis or are protected from fibrosis development. Studies of these mice shed light on the cell types, cell interactions, molecules, and pathways that contribute to SSc manifestations. High-throughput discovery technologies such as DNA microarrays in animal models can identify novel genes and regulatory networks that are important for disease manifestations and that may be targets for therapy. In this brief review, we highlight recent progress in the field and attempt to place the strengths and limitations of popular SSc murine models in perspective.