Mycobacterium paratuberculosis monoassociated nude mice as a paratuberculosis model

Area of Science:

• Veterinary Medicine
• Microbiology
• Immunology

Background:

• Paratuberculosis, also known as Johne's disease, is a chronic infectious disease affecting ruminants.
• Existing research models for paratuberculosis have limitations in replicating the full spectrum of the disease.

Purpose of the Study:

• To develop and characterize a novel animal model for paratuberculosis (Johne's disease) in gnotobiotic athymic nude mice.
• To evaluate the progression of Mycobacterium paratuberculosis infection, including shedding, pathology, and clinical signs.

Main Methods:

• Gnotobiotic athymic nude mice were intragastrically inoculated with Mycobacterium paratuberculosis.
• Fecal shedding, bacterial recovery from tissues (ileum, cecum, colon, liver), histopathology, and clinical signs were monitored over time.
• Tumor necrosis factor activity was assessed in response to lipopolysaccharide challenge.

Main Results:

• Progressive fecal shedding and multiplication of M. paratuberculosis were observed, increasing significantly after 4 months.
• Histopathologic lesions and bacillary loads increased with infection duration, with severe granulomatous inflammation noted in mice infected for 7+ months.
• Five mice developed clinical signs (weight loss, diarrhea), and three succumbed to the infection, mimicking natural Johne's disease.

Conclusions:

• The developed mouse model effectively replicates key features of paratuberculosis, including progressive infection, shedding, and clinical manifestations.
• This model provides a valuable platform for investigating immunoregulation and testing antimicrobial therapies for paratuberculosis.
• The model's consistency with naturally occurring Johne's disease in ruminants enhances its utility for translational research.