The tight skin 2 mouse
Article first published online: 9 DEC 2005
Copyright © 1995 American College of Rheumatology
Arthritis & Rheumatism
Volume 38, Issue 12, pages 1791–1798, December 1995
How to Cite
Christner, P. J., Peters, J., Hawkins, D., Siracusa, L. D. and Jiménez, S. A. (1995), The tight skin 2 mouse. Arthritis & Rheumatism, 38: 1791–1798. doi: 10.1002/art.1780381212
- Issue published online: 9 DEC 2005
- Article first published online: 9 DEC 2005
- Manuscript Revised: 31 JUL 1995
- Manuscript Accepted: 31 JUL 1995
- Manuscript Received: 5 APR 1995
- NIH. Grant Number: R01-A R-3 2564
Objective. To describe the histopathologic and biochemical characteristics of skin from the Tsk2/ + mouse, a mutation with phenotypic features resembling those of systemic sclerosis (SSc), and to report the initial genetic mapping of the Tsk2 locus.
Methods. Histologic examination was performed and collagen content and type I collagen messenger RNA (mRNA) levels were determined in skin biopsy specimens from Tsk2/+ mice and normal mice. An intersubspecific backcross was conducted as a first step toward identifying the position of the Tsk2 locus on mouse chromosome 1.
Results. Histologic examination of Tsk2/+ mouse skin revealed marked accumulation of collagen and infiltration with mononuclear cells in the dermis and adipose tissue. Biochemical studies of Tsk2/+ mouse skin showed increased collagen content and elevated steady-state levels of α1(I) procollagen mRNA. Tsk2 was mapped to a 15.3-c entimorgan interval on mouse chromosome 1.
Conclusion. Tsk2 is a novel mutation which displays histopathologic and biochemical abnormalities similar to those present in the skin of patients with SSc, including increased collagen content and expression of type I collagen genes. This mutation has been mapped to a 15.3-c M region on mouse chromosome 1. Further study of this novel mutation will allow the identification of previously undescribed mechanisms involved in the regulation of normal and pathologic collagen gene expression.