A Clinical Scoring Systems for the Evaluation of Corynebacterium bovis -associated Disease in NSG Mice.

Clinical signs of Corynebacterium bovis infections are well-known in athymic nude mice. However, C. bovis can also infect and cause clinical signs in many hirsute, immunocompromised mouse strains such as NSG (NOD. Cg-Prkdcscid Il2rgtm1Wgl/SzJ). Typically, the clinical assessment of C. bovis-infected mice begins when overt clinical signs are initially observed and thus the early course of infection has not been thoroughly described. The goal of this study was to characterize the clinical progression of C. bovis infection in NSG mice under experimental conditions and develop a quantifiable clinical scoring system. For the development and application of this clinical scoring system, 54 naïve NSG mice were exposed to soiled bedding from clinically ill C. bovis-infected NSG mice and the emergence of clinical signs was monitored and scored weekly for 8 wk. Overall, we identified 6 benchmark changes associated with C. bovis clinical infection. Four changes were the appearance of the eyes, ears, hair coat, and posture. Two behavioral changes were increased grooming activity and rapid head shaking. All clinical signs appeared consistently and progressed temporally with increasing clinical severity. Characterization of clinical signs and scoring of clinical disease will aid veterinarians in the assessment of C. bovis-infected NSG mice and may help in the evaluation of current and future clinical interventions used to prevent or treat C. bovis-infected immunodeficient mice.

Metaphylactic Antibiotic Treatment to Prevent the Transmission of Corynebacterium bovis to Immunocompromised Mouse Offspring.

Current methods for eradicating Corynebacterium bovis, such as depopulation, embryo transfer, and cesarean rederivation followed by cross fostering, are expensive, complex, and time-consuming. We investigated a novel method to produce immunocompromised offspring free of C. bovis from infected NOD. Cg-PrkdcscidIl2rgtm1Wgl/SzJ (NSG) breeding pairs. Adult NSG mice were infected with C. bovis, paired, and randomly assigned to either a no-antibiotic control group (NAB, n = 8) or a group that received amoxicillin-clavulanic acid (0.375 mg/mL) in their drinking water for a mean duration of 7 wk (AB group, n = 7), spanning the time from pairing of breeders to weaning of litters. The AB group also underwent weekly cage changes for 3 wk after pairing to decrease intracage C. bovis contamination, whereas the NAB mice received bi-weekly cage changes. Antibiotics were withdrawn at the time of weaning. All litters (n = 7) in the AB group were culture- and qPCR-negative for C. bovis and remained negative for the duration of the study, whereas all litters in the NAB group (n = 6) remained C. bovis positive. A single adult from each breeding pair was sampled at weaning and at 5 and 10 wk after weaning to confirm the maintenance of (NAB) or to diagnose the reemergence (AB) of C. bovis infection. By the end of the study, C. bovis infection had returned in 3 of the 7 (43%) tested AB adults. Our data suggest that metaphylactic antibiotic use can decrease viable C. bovis organisms from adult breeder mice and protect offspring from infection. However, using antibiotics with frequent cage changing negatively affected breeding performance. Nevertheless, this technique can be used to produce C. bovis-free NSG offspring from infected adults and may be an option for salvaging infected immunocompromised strains of mice that are not easily replaced.