Abstract
The Tight Skin mouse is a genetically induced animal model of tissue fibrosis caused by a large in-frame mutation in the gene encoding fibrillin-1 (Fbn-1). We examined the influence of gender on the collagen content of tissues in C57BL/6J wild type (+/+) and mutant Tight Skin (Tsk/+) mice employing hydroxyproline assays. Tissue sections were stained with Masson's trichrome to identify collagen in situ. Adult Tsk/+ mice skin contains ~15% more collagen, on average, than skin from +/+ mice of the same gender. The heart of Tsk/+ males had significantly more collagen than that of +/+ males. No significant gender differences were found in lungs and kidney collagen content. Overall, the collagen content of Tsk/+ males and +/+ males was higher than that of their Tsk/+ and +/+ female counterparts, respectively. Our data confirm increased deposition of collagen in skin and hearts of Tsk/+ mice; however, the effects of the Tsk mutation on collagen content are both tissue specific and gender specific. These results indicate that comparative studies of collagen content between normal and Tsk/+ mice skin and internal organs must take into account gender differences caused by expression of the androgen receptor.
Highlights
Systemic sclerosis (SSc, scleroderma) is a systemic autoimmune disease of unknown etiology characterized by excessive accumulation of collagen in the skin and internal organs, including the gastrointestinal tract, lungs, heart, and kidneys [1]
We report in this paper quantitative measurements of total collagen content in skin, lung, heart, and kidney samples from Tight Skin (Tsk)/+ mice compared to wildtype +/+ mice, with special emphasis on the importance of controlling for age, gender, and genetic background
Our results indicate that the large differences in collagen content between normal and Tsk/+ mice skin reported in some previous studies may reflect age and gender differences rather than the direct effect of the mutation
Summary
Systemic sclerosis (SSc, scleroderma) is a systemic autoimmune disease of unknown etiology characterized by excessive accumulation of collagen in the skin and internal organs, including the gastrointestinal tract, lungs, heart, and kidneys [1]. The etiologic factors involved in the development and progression of SSc are still unclear study of animal models of the disease is likely to provide valuable information about its pathogenesis and allow identification of potentially effective therapeutic approaches. Tight Skin (Tsk) and Tight Skin 2 (Tsk2), recapitulate some, but not all, features of this disease [3, 4]. Several other features in Tsk/+ mice include an enlarged skeleton and increased cartilage growth, emphysematous lungs, myocardial hypertrophy, and the presence of smaller tendons with tendon sheath hyperplasia [7,8,9]. Molecular analysis of Tsk/+ mice revealed a large, in-frame genomic duplication in the fibrillin-1 gene (Fbn-1) that includes exons 17–40 [11] and results in a mutant Fbn-1 transcript that is 3 kb larger than the wild type Fbn-1 transcript
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