Humanized Model for Spontaneous Autoimmune Myocarditis
Description: Myocarditis is a major cause of sudden death in children and young adults and is often a precursor of dilated cardiomyopathy, a common indication for cardiac transplantation. Myocarditis presents a challenging clinical problem because it is hard to diagnose and the treatment options are limited. It has been widely thought that autoimmune myocarditis is of infectious etiology, and to date, all animal models have involved experimental induction of disease, either by infection with cardiotropic viruses or by immunization with adjuvants containing cardiac myosin. The inventors have created three lines of transgenic NOD mice that express human HLA-DQ8, resulting in the development of spontaneous myocarditis in all three lines. This was associated with premature death by heart failure, lymphocytic infiltrates in myocardial tissues, and cardiac myosin IgG autoantibodies. While the disease process was similar in all lines, its severity differed and correlated with the cell-type specific patterns of HLA-DQ8 expression. Clinical & Commercial Utility: The technology features transgenic mice expressing human HLA-DQ8, which are models of autoimmune myocarditis. Like human patients, these mice develop sudden symptoms of heart failure associated with destructive lymphocytic infiltrates in the myocardium, show histology that is characteristic of myocarditis, and develop autoantibodies that recognize cardiac myosin, a major autoantigen in human myocarditis. These mice should provide a new system for the study of the pathogenic mechanisms of myocarditis and the role of HLA-DQ8 in the disease process.A manuscript describing this research has been accepted for publication in the Journal of Immunology.
Type of Offer: Licensing
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