HYPERKERATOSIS IN ATHYMIC NUDE-MICE CAUSED BY A CORYNEFORM BACTERIUM - MICROBIOLOGY, TRANSMISSION, CLINICAL SIGNS, AND PATHOLOGY

The purpose of this study was to characterize a spontaneous disease condition causing hyperkeratosis in nude mice and to explore the etiologic role of a particular species of coryneform bacteria in this disease, colloquially known as ''scaly skin disease.'' The study was divided into two parts. In the first phase, a series of inoculation experiments was conducted with a field isolate of the coryneform species used to study the clinical and histopathologic development of the disease syndrome. Athymic nude mice (4 to 5 weeks old) were inoculated on the skin of the back with a suspension of a pure culture of the coryneform bacterium that had been isolated from a held ease. The culture was applied with a sterile cotton swab in concentrations varying from 6.1 x 10(4)/ml to 5.0 x 10(7)/ml. Ah inoculated mice became persistently infected throughout the 33 days of the experiment. Clinically evident hyperkeratosis in inoculated animals developed more frequently in mice housed in a microisolator cage than in a semi rigid isolator and more frequently in mice inoculated with higher numbers of organisms. In all animals in which hyperkeratosis developed, it was first noted on day 7 after inoculation. The second series of experiments was designed to determine the success of various housing methods in excluding the infection, mechanisms of transmission, susceptibility of other stocks and strains of mice to the organism, and whether the other strains might serve as a source of the organism. Results of the study in various strains indicated that both immunocompetent and immunodeficient mice, whether glabrous or hirsute, could be infected with the organism, but only glabrous animals developed hyperkeratosis. Infection was transmitted by direct body contact of uninfected mice with infected mice and through fomites (latex gloves). Skin culture and buccal cultures were effective in demonstrating the organism. Histologically, lesions were similar in spontaneous cases, in the inoculation studies, and in the transmission experiments. Histopathologic changes were characterized by marked acanthosis, moderate hyperkeratosis, and a scant mononuclear cell infiltrate. Gram staining demonstrated numerous gram-positive bacteria in the stratum corneum and occasionally in hair follicles. The acanthosis persisted after hyperkeratosis was no longer grossly evident. The bacteria were often arranged in palisading or irregularly branching angular arrays similar to those of Corynbacterium spp. Analysis of the organism disclosed a biochemical and fatty acid profile consistent with the genus Corynebacterium but distinct from other Corynebacterium spp. The descriptive term hyperkeratosis-associated coryneform (HAC) is suggested for the organism. Present studies confirm HAC as a cause of bacterial hyperkeratosis in nude mice and suggest that fomites and asymptomatic carriers, including immunocompetent hirsute mice, may serve as a source of HAC infection in the laboratory animal environment.