Strategies to Prevent, Treat, and Provoke Corynebacterium-Associated Hyperkeratosis in Athymic Nude Mice

Corynebacterium-associated hyperkeratosis (CAH), commonly known as ‘scaly skin disease,’3,5,10,27 has anecdotally been reported as early as 1976 in athymic nude mice,5 with subsequent global outbreaks described in the 1980s and 1990s.5,11,25,27 The predominant clinical sign of the disease is yellow–white keratin flakes adherent to the skin,5,27 with acanthosis, orthokeratotic hyperkeratosis, and a mononuclear cell infiltrate evident on histologic examination of the skin.5,27 A similar disease has been reported in furred immunodeficient mice that includes alopecia and a lesser degree of adherent white keratin flakes on the skin.28 In 1998, the causative agent was identified as Corynebacterium bovis by using 16S rRNA sequence analysis.8,26 C. bovis remains a commonly encountered pathogen in athymic nude mouse colonies at academic and industry vivaria, as determined through personal communication with affected institutions. Bacterial control and elimination from colonies in academic animal care programs can be quite challenging, because depopulation and restricted colony access are often not options. Literature regarding the management of C. bovis is sparse, including variable eradication success with colony depopulation and disinfection27 and mention of a nondescript antibiotic treatment.25 Strategies of antibiotic prophylaxis, various treatments to ameliorate disease, or prolonged antibiotic administration to eradicate subclinical infection have not been reported in the literature. Further, provocation of disease to better understand disease manifestation has not been reported. We sought to better manage this disease as a result of a recent increased incidence of cases characterized by persistent skin lesions, loss of body condition, and increased mortality in athymic nude mice at our institution. Our study centered on 4 hypotheses: (1) antibiotic prophylaxis would provide the immune system time to mount an effective response and prevent clinical disease but not C. bovis infection; (2) various antibiotic treatments would affect clinical disease severity or duration; (3) prolonged antibiotic administration would eradicate C. bovis infection from athymic nude mice; and (4) provocation testing would elicit severe disease mimicking that previously seen in our vivarium. Our findings provide a foundation on which further C. bovis management strategies can be developed.