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 hyperg...

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Main Authors: Takuma Hayashi, Motoki Ichikawa, Ikuo Konishi
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/10/6/1443
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author Takuma Hayashi
Motoki Ichikawa
Ikuo Konishi
author_facet Takuma Hayashi
Motoki Ichikawa
Ikuo Konishi
author_sort Takuma Hayashi
collection DOAJ
description 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-κB1) (also known as p50) in the development of type 1 diabetes was investigated. In response to these arguments, NOD mice with inconsistent NF-κB1 expression were established. Surprisingly, the majority of NOD <i>Nfκb1</i> 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 <i>Nfκb1</i> heterozygote mice as early as 4 months of age. Additionally, in NOD <i>Nfκb1</i> 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 <i>Nfκb1</i> heterozygote mice can be used for investigating the risk of myocarditis development after vaccination.
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spelling doaj.art-5b4dbdf7ee494b2bbf245236cc59ad9d2023-11-23T15:44:56ZengMDPI AGBiomedicines2227-90592022-06-01106144310.3390/biomedicines10061443Spontaneous Myocarditis in Mice Predisposed to Autoimmune Disease: Including Vaccination-Induced OnsetTakuma Hayashi0Motoki Ichikawa1Ikuo Konishi2School of Medicine, Shinshu University, Nagano 390-8621, JapanSchool of Medicine, Shinshu University, Nagano 390-8621, JapanNational Hospital Organization Kyoto Medical Centre, Kyoto 612-8555, JapanNonobese 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-κB1) (also known as p50) in the development of type 1 diabetes was investigated. In response to these arguments, NOD mice with inconsistent NF-κB1 expression were established. Surprisingly, the majority of NOD <i>Nfκb1</i> 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 <i>Nfκb1</i> heterozygote mice as early as 4 months of age. Additionally, in NOD <i>Nfκb1</i> 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 <i>Nfκb1</i> heterozygote mice can be used for investigating the risk of myocarditis development after vaccination.https://www.mdpi.com/2227-9059/10/6/1443myocarditisNF-κB1vaccinenonobese diabetic (NOD)autoimmune disease
spellingShingle Takuma Hayashi
Motoki Ichikawa
Ikuo Konishi
Spontaneous Myocarditis in Mice Predisposed to Autoimmune Disease: Including Vaccination-Induced Onset
Biomedicines
myocarditis
NF-κB1
vaccine
nonobese diabetic (NOD)
autoimmune disease
title Spontaneous Myocarditis in Mice Predisposed to Autoimmune Disease: Including Vaccination-Induced Onset
title_full Spontaneous Myocarditis in Mice Predisposed to Autoimmune Disease: Including Vaccination-Induced Onset
title_fullStr Spontaneous Myocarditis in Mice Predisposed to Autoimmune Disease: Including Vaccination-Induced Onset
title_full_unstemmed Spontaneous Myocarditis in Mice Predisposed to Autoimmune Disease: Including Vaccination-Induced Onset
title_short Spontaneous Myocarditis in Mice Predisposed to Autoimmune Disease: Including Vaccination-Induced Onset
title_sort spontaneous myocarditis in mice predisposed to autoimmune disease including vaccination induced onset
topic myocarditis
NF-κB1
vaccine
nonobese diabetic (NOD)
autoimmune disease
url https://www.mdpi.com/2227-9059/10/6/1443
work_keys_str_mv AT takumahayashi spontaneousmyocarditisinmicepredisposedtoautoimmunediseaseincludingvaccinationinducedonset
AT motokiichikawa spontaneousmyocarditisinmicepredisposedtoautoimmunediseaseincludingvaccinationinducedonset
AT ikuokonishi spontaneousmyocarditisinmicepredisposedtoautoimmunediseaseincludingvaccinationinducedonset