Identification of the Gene for Scleroderma in the Tsk/2 Mouse Strain: Implicationsfor Human Scleroderma Pathogenesis and Subset Distinctions
Abstract
This project focuses on an animal model of the human disease, systemic sclerosis (SSc), called Tsk2/+. The SSc-like traits in Tsk2/+ heterozygotes are highly penetrant. In addition to a readily apparent skin fibrosis resulting from ECM anomalies, Tsk2/+ mice show autoimmune and inflammatory features that closely resemble human SSc features, making it useful as a pre-clinical model. In this report, we show a clear time dependence on the gene expression in the skin of the Tsk2/+ mice. We have proven that Col3a1 is the gene that causes Tsk2/+ fibrosis, and have confirmed the sequence difference between Tsk2/+ and the parent strain, 101. We present preliminary results on the expression of TGF -dependent mRNA signatures from Tsk2/+ and WT littermates that suggest the mechanism for the fibrosis is related to the up-regulation of TGF signatures seen in the mutant strain. We show that Col3A1 fibers are altered in aged Tsk2/+ mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2013
- Accession Number
- ADA593290
Entities
People
- Carol Artlett
- Elizabeth P. Blankenhorn
- Michael Whitfield
Organizations
- Drexel University