Spontaneous Myocarditis in Mice Predisposed to Autoimmune Disease: Including Vaccination-Induced Onset

Nonobese diabetic (NOD)/ShiLtJ mice, such as biobreeding rats, are used as an animal model for type 1 diabetes. Diabetes develops in NOD mice as a result of insulitis, a leukocytic infiltrate of the pancreatic islets. The onset of diabetes is associated with moderate glycosuria and nonfasting hyperglycemia. Previously, in NOD/ShiLtJ mice spontaneously developing type 1 diabetes, the possible involvement of decreased expression of nuclear factor-kappa B1 (NF-kappa B1) (also known as p50) in the development of type 1 diabetes was investigated. In response to these arguments, NOD mice with inconsistent NF-kappa B1 expression were established. Surprisingly, the majority of NOD Nf kappa b1 homozygote mice were found to die by the eighth week of life because of severe myocarditis. The incidence of spontaneous myocarditis in mice was slightly higher in males than in females. Furthermore, insulitis was observed in all NOD Nf kappa b1 heterozygote mice as early as 4 months of age. Additionally, in NOD Nf kappa b1 heterozygote mice, myocarditis with an increase in cTnT levels due to influenza or hepatitis B virus vaccination was observed with no significant gender difference. However, myocarditis was not observed with the two types of human papillomavirus vaccination. The results of immunological assays and histopathological examinations indicated that vaccination could induce myocarditis in genetically modified mice. In this study, we report that NOD Nf kappa b1 heterozygote mice can be used for investigating the risk of myocarditis development after vaccination.

Automated summary

NOD/ShiLtJ mice are used as an animal model for type 1 diabetes. Decreased expression of nuclear factor-kappa B1 (NF-kappa B1) may be involved in the development of type 1 diabetes. Genetically modified NOD Nf kappa b1 homozygote mice were found to develop severe myocarditis, while NOD Nf kappa b1 heterozygote mice developed early insulitis. Vaccination could induce myocarditis in genetically modified mice.