The development of fatal myocarditis and polymyositis in mice heterozygous for IFN-γ and lacking the SOCS-1 gene
D Metcalf, L Di Rago, S Mifsud, L Hartley… - Proceedings of the …, 2000 - pnas.org
D Metcalf, L Di Rago, S Mifsud, L Hartley, WS Alexander
Proceedings of the National Academy of Sciences, 2000•pnas.orgMice lacking the gene encoding the suppressor of cytokine signaling-1 (SOCS-1−/−) and
heterozygous for the IFN–γ gene (IFN-γ+/−) avoided the IFN-γ-dependent preweaning death
of SOCS-1−/− IFN-γ+/+ mice but did not exhibit the good health of young adult SOCS-1−/−
IFN-γ−/− mice. SOCS-1−/− IFN-γ+/− mice died within 160 days of birth with massive T
lymphocyte, macrophage, and eosinophil infiltration of all skeletal muscles and a similar
severe myocarditis. The cornea also developed inflammatory infiltration and often a corneal …
heterozygous for the IFN–γ gene (IFN-γ+/−) avoided the IFN-γ-dependent preweaning death
of SOCS-1−/− IFN-γ+/+ mice but did not exhibit the good health of young adult SOCS-1−/−
IFN-γ−/− mice. SOCS-1−/− IFN-γ+/− mice died within 160 days of birth with massive T
lymphocyte, macrophage, and eosinophil infiltration of all skeletal muscles and a similar
severe myocarditis. The cornea also developed inflammatory infiltration and often a corneal …
Mice lacking the gene encoding the suppressor of cytokine signaling-1 (SOCS-1 −/−) and heterozygous for the IFN–γ gene (IFN-γ +/−) avoided the IFN-γ-dependent preweaning death of SOCS-1 −/− IFN-γ +/+ mice but did not exhibit the good health of young adult SOCS-1 −/− IFN-γ −/− mice. SOCS-1 −/− IFN-γ +/− mice died within 160 days of birth with massive T lymphocyte, macrophage, and eosinophil infiltration of all skeletal muscles and a similar severe myocarditis. The cornea also developed inflammatory infiltration and often a corneal ulcer. The mice exhibited evidence of selective CD8 T lymphocyte activation in populations in the thymus, spleen, and lymph nodes and focal T- and B-lymphoid infiltrates developed in the lung and salivary gland without apparent tissue damage. Comparison of SOCS-1 −/− IFN-γ +/− mice with various control mice indicated that the development of tissue-damaging T lymphocyte, macrophage, and eosinophil infiltrates required loss of SOCS-1 and the presence of some IFN–γ, but that the lung lymphoid infiltrates required only loss of SOCS-1 to develop.
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