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Detailed mechanistic study of systemic sclerosis (SS) has suffered from a lack of animal models that recapitulate the key clinical findings of this disease. Finding that fibrillin 1 (FBN1) is mutated in familial stiff skin syndrome (SSS), another pathological skin fibrosis, Gerber and colleagues created a mouse model based on two mutations in the gene. Integrins are multifunctional proteins that anchor cells to the extracellular matrix (hemidesmosomes) and regulate the secretion of cytokines such as transforming growth factor β (TGFβ). When fibrillin 1 fails to interact with integrins, unrestrained TGFβ pathway activation leads to fibrosis.
To directly test the role of integrin–fibrillin-1 interactions, the investigators generated mice with …