Regulation of collagen gene expression in the Tsk2 mouse
Article first published online: 24 OCT 2007
Copyright © 2007 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 215, Issue 2, pages 464–471, May 2008
How to Cite
Barisic-Dujmovic, T., Boban, I. and Clark, S. H. (2008), Regulation of collagen gene expression in the Tsk2 mouse. J. Cell. Physiol., 215: 464–471. doi: 10.1002/jcp.21319
- Issue published online: 21 FEB 2008
- Article first published online: 24 OCT 2007
- Manuscript Accepted: 13 SEP 2007
- Manuscript Received: 25 JUL 2007
- National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grant Number: R01 AR048082
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.