Animal models (ICR model) with HSV

SOHN Seonghyang

Purpose

Behçet’s disease (BD) is a chronic systemic inflammatory disease characterized by relapses of mouth ulcers, genital ulcers, skin inflammation, and uveitis. Although the pathogenesis of BD is not fully understood, genetically susceptible responses to environmental factors such as microbiome, HSV infection and immunological abnormalities are considered to cause BD. Appropriate disease animal models are useful for disease studies, so we developed a BD model.

Methods

After scratching the earlobe of ICR mouse and inoculating twice with herpes simplex virus type 1 (HSV-1) at 10-day intervals, follow-up for more than 16 weeks showed BD-like symptoms.

Results

Symptoms in mice were very similar to those in human patients, such as skin ulcers, genital ulcers, and eye inflammation. In addition, minor BD symptoms such as arthritis and intestinal involvement were also observed. The prevalence of mice maintained under specific pathogen-free and conventional breeding facilities differed significantly, suggesting a microbiome relationship. Stress in conventional rearing conditions increased the prevalence of BD. In ICR model, the therapeutic effects of colchicine, pentoxifylline, infliximab, etanercept, and abatacept were tested, and potential therapeutic candidates such as IL-6 siRNA and TNFα siRNA were also applied. Microbiome correlations were studied with this model. Symptoms could be controlled by specific gut bacteria and the short-chain fatty acids they secrete.

Conclusions

To date, the HSV-induced BD mouse model has been consistently used since it was first reported as it exhibits symptoms most similar to those seen in BD patients. It is expected that this mouse model will be useful to find more effective treatments to overcome this disease.




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