The Relaxin Gene Knockout Mouse: A Model of Progressive Scleroderma

• Published in: Journal of investigative dermatology Vol. 125; no. 4; pp. 692 - 699
• Main Authors: Samuel, Chrishan S., Zhao, Chongxin, Yang, Qing, Wang, Hong, Tian, Hongsheng, Tregear, Geoffrey W., Amento, Edward P.
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01-10-2005; Nature Publishing; Elsevier Limited
• Subjects: Animals; Biological and medical sciences; collagen; Collagen - analysis; Collagen - metabolism; dermal fibrosis; Disease Models, Animal; Female; Fibrosis; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Relaxin - deficiency; Relaxin - genetics; Relaxin - physiology; relaxin-deficient mice; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; scleroderma; Scleroderma, Diffuse - etiology; Scleroderma, Diffuse - metabolism; Scleroderma, Diffuse - pathology; Skin - chemistry; Skin - pathology; collagen; relaxin-deficient mice; dermal fibrosis; scleroderma; Connective tissue disease; Animal model; Skin disease; Dermatology; Deficiency; Peptide hormone; Rodentia; Autoimmune disease; collagen/dermal fibrosis/relaxin-deficient mice/scleroderma; Relaxin; Vertebrata; Mammalia; Gene; Mouse; Collagen; Systemic disease; Fibrosis; Knockout mouse; Genetics; Derm; Scleroderma
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/j.0022-202X.2005.23880.x

Relaxin is a peptide hormone with anti-fibrotic properties. To investigate the long-term effects of relaxin deficiency on the ageing skin, we compared structural changes in the skin of ageing relaxin-deficient (RLX-/-) and normal (RLX+/+) mice, by biochemical, histological, and magnetic resonance imaging analyses. Skin biopsies from RLX+/+ and RLX-/- mice were obtained at different ages and analyzed for changes in collagen expression and distribution. We demonstrated an age-related progression of dermal fibrosis and thickening in male and female RLX-/- mice, associated with marked increases in types I and III collagen. The increased collagen was observed primarily in the dermis of RLX-/- mice by 1 mo of age, and eventually superseded the hypodermal layer. Additionally, fibroblasts from the dermis of RLX-/- mice were shown to produce increased collagen in vitro. Recombinant human gene-2 (H2) relaxin treatment of RLX-/- mice resulted in the complete reversal of dermal fibrosis, when applied to the early onset of disease, but was ineffective when applied to more established stages of dermal scarring. These combined findings demonstrate that relaxin provides a means to regulate excessive collagen deposition in disease states characterized by dermal fibrosis and with our previously published work demonstrate the relaxin-null mouse as a model of progressive scleroderma.