Abstract
Ulcerative Dermatitis (UD) is the most common cause of unplanned euthanasia in mice used in research, with prevalence rates reported between 4 and 21%. UD is characterized by a deep, ulcerative lesion that appears most commonly over the dorsal neck and is attendant with an intense pruritus. The underlying cause of UD is currently unknown, and as a consequence, there are no directed therapies that resolve lesions reliably. However, there is a growing body of evidence that suggests a behavioral component to the onset, maintenance, and progression of UD lesions. Scratching behavior in response to the intense pruritus associated with UD lesions may be an effective target for interventional therapies. We hypothesized that interfering with scratching behavior by trimming the toenails of mice with UD, would resolve UD lesions. To test this hypothesis, we first evaluated the efficacy of toenail trims with a single application of Vetericyn at the time of treatment versus our previous standard of care, topical Tresaderm applied daily. We found that toenail trims were significantly more effective at resolving lesions (n = 39 toenail trims, n = 100 Tresaderm, p<0.0001) with 93.3% of animals healing by 14 days (median time to lesion resolution). Furthermore, dorsal neck lesions did not recur by 42 days after a single toenail trim (n = 54); however, flank lesions did not resolve and the outcome of the two lesion distributions following treatment were significantly different (p<0.0001). Finally, we implemented toenail trims at an institutional level and found similar efficacies (approximately 90%) for toenail trims regardless of one-time topical supplement used (triple antibiotic ointment, Tresaderm, and Vetericyn, n = 55, 58, 18, p = 0.63). This is the first report of a highly effective treatment for one of the most serious welfare issues in laboratory mice.
Highlights
Ulcerative Dermatitis (UD) of mice is a pervasive condition commonly seen in mouse research facilities
Logistic regression showed that the cure rate for mice receiving toenail trim (93.3% +/- 4.1%) was significantly higher than those receiving Tresaderm (25.4% +/- 4.8%) (Likelihood-Ratio ChiSquare = 44.26; P < 0.0001; Fig 2)
In the final aim of our study, implementing toenail trimming at an institutional level by our technicians, we addressed this finding by considering UD flank lesions a grave prognosis and grounds for immediate euthanasia
Summary
Ulcerative Dermatitis (UD) of mice is a pervasive condition commonly seen in mouse research facilities. The nature of the wounds, the lack of effective treatment, and the resulting euthanasia rate, UD is one of the most important welfare issues in laboratory mice. Lesions have a distinctive appearance and are characterized by deep, ulcerative wounds that appear with specific body distributions—most commonly the dorsal neck, followed by facial, flank, limb and other locations [1]. These lesions are coincident with an intense pruritus eliciting up to 25 scratching bouts per minute [4]. For all of these associations, the trigger that incites lesion appearance is not clearly identified and is likely multifactorial in nature
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