%0 Journal Article
%T Collagen Content in Skin and Internal Organs of the Tight Skin Mouse: An Animal Model of Scleroderma
%A Jayanthi Manne
%A Marina Markova
%A Linda D. Siracusa
%A Sergio A. Jimenez
%J Biochemistry Research International
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/436053
%X 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. 1. Introduction 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]. Besides the often progressive fibrotic process, the pathogenesis of this disorder is characterized by severe microvascular alterations and distinct immunological abnormalities in cellular and humoral responses [2]. The etiologic factors involved in the development and progression of SSc are still unclear thus, study of animal models of the disease is likely to provide valuable information about its pathogenesis and allow identification of potentially effective therapeutic approaches. Mammalian model systems that reproduce all the features of human SSc are not available. Two spontaneous mouse mutations, Tight Skin (Tsk) and Tight Skin 2 (Tsk2), recapitulate some, but not all, features of this disease [3, 4]. The Tsk mutation occurred spontaneously in the inbred mouse strain B10.D2(58N)/Sn [5]. Homozygous Tsk/Tsk mice die in utero by day 8 of gestation, while heterozygous Tsk/+ mice survive to adulthood. Tsk/+ mice have thickened skin which is bound tightly to subcutaneous tissue under the dermis and lacks the pliability and elasticity of normal skin [5, 6]. Several other features in Tsk/+ mice include an
%U http://www.hindawi.com/journals/bri/2013/436053/