Spontaneous myocarditis in mice predisposed to autoimmune disease: Including Vaccination-induced onset

Non-obese diabetic (NOD)/ShiLtJ mice, like 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 a moderate glycosuria and a non-fasting hyperglycemia. Previously, in non-obese diabetic (NOD)/ShiLtJ mice spontaneously developing type 1 diabetes, the possible involvement of decreased expression of LMP2/β1i, an immunoproteasome β subunit, and associated decreased expression of NF-κB1 (also called as p50) in the development of type 1 diabetes was argued between our research team and other research groups. In response to these arguments, we created NOD mice in which NF-κB1 expression is not consistently observed. Unexpectedly, most NOD Nfκb1 homozygote mice were found to die by the 8th week of age due to the development of severe myocarditis. Furthermore, in all NOD Nfκb1 heterozygote mice, the onset of Insulitis was observed from 4 months of age. In addition, in NOD Nfκb1 heterozygote mice, an increase in cTnT due to vaccination with influenza or HBV vaccine was observed without gender difference. Now, we found a direct involvement of decreased expression of NF-κB1 in the development of autoimmune diseases in NOD/ShiLtJ mice. Therefore, we would like to introduce new research results on autoimmune diseases, including findings on important risk factors for the development of myocarditis observed after vaccination with mRNA-based COVID-19 vaccine.