Animal Models for Autoimmune Myocarditis and Autoimmune Thyroiditis(1)
The following introduces three animal disease models: two autoimmune myocarditis and one autoimmune thyroiditis, which can be induced in general mouse strains.
Autoimmune myocarditis can be induced by Choxackie virus B3 (CB3) infection in genetically susceptible mouse strains, which closely resembles the course of human myocarditis. Cardiac myosin-induced myocarditis (EAM) and cardiac alpha-myosin heavy chain peptide-induced myocarditis are known as antigen induced disease models. The EAM models show similar histological changes and genetic susceptibilities with the CB3 model.
Autoimmune Thyroiditis (EAT) can be induced by immunization of mouse thyroglobulin in CFA or lipopolysaccharide in genetically susceptible mouse strains who carry H-2Ak, H-2As or H-2Aq alleles.
The CB3 model shows two phases of infection and only genetically susceptible mice proceed to the chronic stage of the disease. The early, acute phase of CB3 model develops in many mouse strains, however, the late, chronic stage is shown in Balb/c mice which develops from day 28 and persists to at least day 56. The models induce IgM and IgG autoantibodies against cardiac myosin in both susceptible and resistant mouse strains. However, the susceptible mice produce higher IgG1 autoantibodies to cardiac myosin than the resistant mice. Thus, the major antigen is mouse cardiac myosin heavy chain with the CB3 model. The myosin purified from mouse hearts can induce EAM by immunization with adjuvants in mice. In addition, alpha myosin heavy-chain peptide sequences also can induce EAM in A/J and Balb/c mice.
After the immunization of antigen (myosin or peptides) with CFA on day 0 and 7, inflammation in the heart appears about day 14, peaking around day 21 then declining but persisting upto day 60. At the end point, fibrosis appears in the heart. Genetic background is important in the EAM model. Mouse strain having “A” background show high susceptible, such as A/J, A/CA, and A.SW. Moderate susceptible strains are Balb/c, and resistant strains are C57BL/10 and C57BL/6. The susceptibility associated with the MHC gene, especially H-2 modifies the severity of disease. Immunization of mouse thyroglobulin with CFA or lipopolysaccharide (LPS) can induce experimental thyroiditis (EAT) in specific mouse strains who carry I-A subregion of H-2. Mouse strains express H-2A-k, q, or s (CBA/1, DBA/1J, SWR/J, A.SW/J or SJL/J) are high susceptible in EAT, but H-2A-a, b, or d (B10.A, C57BL/6J, Balb/c or DBA/2J) are poor responders.