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Scleroderma signs in Tight Skin 2 mice develop progressively over time. (47.25)
Journal article   Peer reviewed

Scleroderma signs in Tight Skin 2 mice develop progressively over time. (47.25)

Kristen Long, Carol Artlett and Elizabeth Blankenhorn
The Journal of immunology (1950), v 186(1_Supplement)
01 Apr 2011
DOI: https://doi.org/10.4049/jimmunol.186.Supp.47.25

Abstract

Abstract Systemic sclerosis (SSc) is an often fatal inflammatory autoimmune disease affecting connective tissue, characterized by excessive collagen deposition in skin and other organs. The Tight Skin (Tsk) 2 mouse model of disease has many features of human disease including tight skin, excessive collagen deposition, alterations in the extracellular matrix, and occurrence of antinuclear antibodies (ANA) with age. Since current treatments only ameliorate disease symptoms, the Tsk2/+ mouse is crucial for the understanding of disease pathology and progression, however, the Tsk2 gene has yet to be elucidated. Our lab has recently narrowed the interval containing the gene to 2.9 megabases. Understanding disease progression in this model is essential, and histological and total protein studies have shown that increased collagen accumulation does not occur until at least 10 weeks of age in Tsk2/+ mice, despite the “tight” phenotype occurring at 2 weeks. mRNA expression levels from the skin of young mice showed that Tsk2/+ mice have an up regulation of Col1a1, Col3a1, and Col5a2, as well as a robust expression of TGF-β signatures and extracellular matrix fibers. Histological studies revealed a significant increase of elastic bundles in the dermis of 2 week old Tsk2/+ mice. Aged Tsk2/+ mice produced ANA specific to severe disease after initial fibrosis, suggesting additional progression of the disease state. Our studies reveal a novel timeline of disease progression in the Tsk2/+ mouse.

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