Severely Impaired Wound Healing in the Collagenase-Resistant Mouse

• Published in: Journal of investigative dermatology Vol. 120; no. 1; pp. 153 - 163
• Main Authors: Beare, Alice H.M., O'Kane, Sharon, Ferguson, Mark W.J., Krane, Stephen M.
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.01.2003; Nature Publishing; Elsevier Limited
• Subjects: Actins - analysis; Animals; Biological and medical sciences; collagen; Collagenases - analysis; Collagenases - physiology; Dermatology; Inflammation - pathology; Investigative techniques, diagnostic techniques (general aspects); Matrix Metalloproteinase 13; matrix metalloproteinases; Medical sciences; Metalloendopeptidases - analysis; Mice; Mice, Inbred C57BL; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Proliferating Cell Nuclear Antigen - analysis; tissue repair; transgenic mice/wound healing; Wound Healing - physiology; Wounds and Injuries - pathology; collagen; matrix metalloproteinases; tissue repair; transgenic mice/wound healing; Enzyme; Rodentia; Metalloendopeptidases; Peptidases; collagen/matrix metalloproteinases/tissue repair/transgenic mice/wound healing; Vertebrata; Experimental disease; Mammalia; Mouse; Animal; Collagen; Endopeptidase; Hydrolases; Extracellular matrix; Cicatrization; Interstitial collagenase
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1046/j.1523-1747.2003.12019.x

Collagen in the skin undergoes dramatic reorganization during wound repair. Matrix metalloproteinases degrade and remodel the collagen in a tightly controlled process. The collagenase-resistant mouse, Col1a1tm1Jae, has been developed to produce collagen type I, which is resistant to degradation by human matrix metalloproteinase 1. These mice grow normally but develop thickened skin with age. We investigated the effect of this mutant collagen on wound repair. Incisional wounds were made on Col1a1tm1Jae homozygous mutant (Col1a1r/r) and wild-type (Col1a1+/+) mice and these wounds were harvested at 1 and 6 h, 1, 2, 3, 7, 10, 14, and 70 d post wounding. Wound healing was severely delayed in Col1a1r/r wounds, with wounds remaining significantly wider than wild-type for the first 2 wk after injury. Reepithelialization of the Col1a1r/r wounds took 7 d longer than in the wild-type. The Col1a1r/r wounds had a prolonged early inflammatory response. Immunostaining for matrix metalloproteinases revealed significant upregulation of matrix metalloproteinase 13 in Col1a1r/r wounds, but minimal changes in other matrix metalloproteinases. There was no significant difference in scarring between Col1a1r/r and Col1a1+/+ wounds after 70 d.