Identification of the Gene for Scleroderma in the Tsk/2 Mouse Strain: Implications for Human Scleroderma Pathogenesis and Subset Distinctions

Abstract

We have shown a clear time dependence on the gene expression in the skin of the Tsk2/+ mice. The mouse most resembles human SSc at a narrowly defined time point (4 wks of age) which means studies that use this model as a surrogate for human SSc, must use specific time points in their analysis. We have pinpointed at least one candidate gene in the interval for Tsk2/+ and have confirmed the sequence difference between Tsk2/+ and the parent strain, 101/H. We present preliminary results on the expression of TGF mRNA from cells cultured on ECM from Tsk2/+ and WT littermates that suggest a mechanism for the up-regulation of TGF seen in the mutant strain. We show that elastin content in the skin, known to be controlled by TGF and possibly up-regulated in SSc is the earliest indicator of tight-skin in the tissue.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2012
Accession Number
ADA569137

Entities

People

  • Carol Artlett
  • Elizabeth Blankenhorn
  • Michael Whitfield

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Cell Physiological Processes
  • Cells
  • Collagen
  • Connective Tissue
  • Diseases And Disorders
  • Dna Microarrays
  • Gene Expression
  • Genes
  • Genetic Phenomena
  • Genetics
  • Growth Factors
  • Identification
  • Intervals
  • Mast Cells
  • Sequences
  • Universities

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