The development of fatal myocarditis and polymyositis in mice heterozygous for IFN-gamma and lacking the SOCS-1 gene.
Mice lacking the gene encoding the suppressor of cytokine signaling-1 (SOCS-1 -/-) and heterozygous for the IFN-gamma gene (IFN-gamma +/-) avoided the IFN-gamma-dependent preweaning death of SOCS-1 -/- IFN-gamma +/+ mice but did not exhibit the good health of young adult SOCS-1 -/- IFN-gamma -/- mice. SOCS-1 -/- IFN-gamma +/- 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-gamma +/- 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-gamma, but that the lung lymphoid infiltrates required only loss of SOCS-1 to develop.
Metcalf
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The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, Post Office, Royal Melbourne Hospital, 3050 Victoria, Australia.
Di Rago
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Mifsud
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Hartley
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Alexander
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WS
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D006579:Heterozygote; D007371:Interferon-gamma / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000235:genetics* / Q000473:pathology; D017285:Polymyositis / Q000235:genetics* / Q000473:pathology; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
D002352:Carrier Proteins; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma