ab225010

Increased dermal elastic fibers in the tight skin mouse

S. Chatterjee, M.E. Mark, P.H. Wooley, W.D. Lawrence, M.D. Mayes

Division of Rheumatology, Department of Internal Medicine; Department of Orthopedic Surgery; and Department of Patho-logy, Wayne State University School of Medicine, Detroit, Michigan, USA

ABSTRACT
Objective
The tight skin (Tsk-1) mouse has been proposed as a model for systemic sclerosis on the basis of increased accumulation of collagen and glycosaminoglycans in the skin, and by the presence of serum autoantibodies. The genetic basis of the mutation has been identified as a genomic duplication within the fibrillin-1 (Fbn-1) gene that results in a larger than normal Fbn-1 transcript, but the mechanism that leads to dermal fibrosis is unclear. Fibrillin molecules associate into a polymer that is coated with elastin molecules to form elastic fibers. To further evaluate the Tsk-1 mouse model of scleroderma, we have studied elastic fibers in the skin of these mice.

Methods
Skin sections obtained from C57BL/6-TSK+ (Tsk-1) and C57BL6-pa/+ (control) mice were stained with Masson's trichrome for evaluation of collagen and Gomori's aldehyde fuchsin stain for elastic tissue. Computer assisted image analysis was performed to quantify differences in histologic sections.

Results
Tsk-1 mice had a highly significant increase in the percentage of elastic fibers (19.6%) in the dermis compared to control mice (7.9%) [p < 0.001]. This correlates with the findings in the skin of systemic sclerosis patients where increased elastic fibers have been observed. In addition, an increased level of dermal collagen staining was also observed in the Tsk-1 dermis (82.9%) compared with the level in normal sections (73.7%) [p<0.01].

Conclusion
These data support the use of the Tsk-1 mouse as a model for the connective tissue abnormalities of human scleroderma.

Key words
Scleroderma, animal models, mice, collagen, elastin.

Please address correspondence and reprint requests to: Soumya Chatterjee, MD, MS, Department of Rheumatic and Immunologic Diseases, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk A-50, Cleveland, Ohio 44195, USA.
E-mail address: soumyac@umich.edu

Note: Interested individuals may contact the author directly to obtain a copy of Figure 1 in colour (digital format).