Regulation of collagen gene expression in the Tsk2 mouse

✍ Scribed by Tatjana Barisic-Dujmovic; Ivana Boban; Stephen H. Clark

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 409 KB
• Volume: 215
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.21319

✦ Synopsis

Abstract

The tight skin 2 (Tsk2) mutation is an ENU induced dominant mutation localized on mouse chromosome 1. While the molecular defect is unknown, Tsk2/+ mice display cutaneous thickening associated with excessive matrix production and are used as a model of scleroderma. The purpose of this study was to examine the cellular mechanisms associated with the excessive synthesis of matrix macromolecules using a collagen promoter GFP reporter transgene (pOBCol3.6GFP) as a marker of Col1a1 expression. This analysis of pOBCol3.6GFP expression in Tsk2/+ skin showed an increase in transgene activity compared to wild‐type (+/+) samples. In addition, an increased area of “high” GFP fluorescence in Tsk2/+ dermis in both 1‐ and 4‐month‐old mice was observed that was also associated with an increased number of dermal fibroblasts per unit area of dermis. These data collectively suggest an important mechanism of Tsk2/+ skin fibrosis; an increased number of collagen expressing cells as well as elevated collagen expression on a per cell basis. During this study it was noted that Tsk2/+ mice appeared consistently smaller than wild‐type (+/+) siblings and measurements of body length revealed a decrease (5–10%) in 1‐ and 2‐month‐old Tsk2/+ mice as well as a decrease in body weight in both age groups as compared to wild‐type (+/+) control mice. Femur length was also decreased (2–9%) in Tsk2/+ mice. Finally, in contrast to Tsk/+ mice that display an emphysema‐like lung pathology, histological sections of lungs from Tsk2/+ mice were normal and indistinguishable from wild‐type (+/+) controls. J. Cell. Physiol. 215: 464–471, 2008. © 2007 Wiley‐Liss, Inc.