Stiff skin syndrome (SSS), a form of scleroderma defined by a pathological fibrosis of the skin, is caused by heterozygous missense mutations in the Arg-Gly-Asp (RGD) integrin-binding domain of the FBN1 (fibrillin 1) gene.
These mice carry a W1572C mutation (equivalent of the human W1570C mutation) in the mouse Fbn1 gene. The mutation is widely expressed in tissues including the skin, aorta, lungs and liver. Heterozygotes serve as a model of human stiff skin syndrome with increased collagen deposition in the dermis by 1 month of age, decreased subcutaneous fat by 3 months of age, disorganized and excessive microfibrillar aggregates in the dermis, and circulating anti-nuclear and anti-topoisomerase I antibodies by three months of age. Mice show skin infiltration of pro-inflammatory immune cells including plasmacytoid dendritic cells, T helper cells, and plasma cells. Mice homozygous for the W1572C mutation are viable and show accelerated skin fibrosis when compared with heterozygous littermates.
