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The TallyHo Polygenic Mouse Model of Diabetes: Implications in Wound Healing

Buck, Donald W. II M.D.; Jin, Da P. B.S.; Geringer, Matthew B.S.; Hong, Seok Jong Ph.D.; Galiano, Robert D. M.D.; Mustoe, Thomas A. M.D.

Plastic and Reconstructive Surgery: November 2011 - Volume 128 - Issue 5 - p 427e–437e
doi: 10.1097/PRS.0b013e31822b7333
Experimental: Original Articles

Background: Impairments in wound healing represent a significant source of morbidity and mortality in patients with diabetes. To help uncover the derangements associated with diabetic wound healing, murine animal models have been extensively used. In this article, the authors present results, and the accompanying wound healing implications, from experiments across three validated wound healing models using a newer polygenic strain of diabetes.

Methods: The authors investigated the wound healing impairments of the TallyHo/JnJ diabetic mouse strain, using three validated wound healing models: an incisional model, a splinted excisional model, and a cutaneous ischemia-reperfusion injury model. Appropriate control strain mice were used for comparison. Wounds were analyzed using gross, histologic, and molecular techniques.

Results: TallyHo mice displayed deficits across all three wound healing models. There was a reduced resistance/response to oxidative stress and a global decrease in the initial inflammatory response to healing. In addition, there was a global decrease in the stimulus for angiogenesis and collagen formation, ultimately leading to reduced reepithelialization, granulation tissue formation, wound contraction, and wound tensile strength. Gross and histologic findings were corroborated with molecular data, which revealed a significant down-regulation of important cytokines, including vascular endothelial growth factor, neutrophilic attractant protein-2, monocyte chemoattractant protien-1, heme oxygenase-1, interleukin-1β, and interleukin-6, when normalized to the control strain (p < 0.05).

Conclusions: The TallyHo polygenic mouse model of diabetes demonstrates predictable and clinically relevant wound healing impairments that offer important implications into the derangements of diabetic wound healing observed clinically. Therapeutics targeting these specific derangements could provide improvements in the care of diabetic wounds.

Chicago, Ill.

From the Laboratory for Wound Repair and Regeneration, Division of Plastic and Reconstructive Surgery, Northwestern University.

Received for publication March 10, 2011; accepted April 12, 2011.

Disclosure:The authors have no financial interest to declare in relation to the content of this article.

Thomas A. Mustoe, M.D.; Division of Plastic and Reconstructive Surgery, Northwestern University, 675 North St. Clair Street, Galter 19-250, Chicago, Ill. 60611,

©2011American Society of Plastic Surgeons