The development of fatal myocarditis and polymyositis in mice heterozygous for IFN-gamma and lacking the SOCS-1 gene
- Author(s)
- Metcalf, D; Di Rago, L; Mifsud, S; Hartley, L; Alexander, WS;
- Details
- Publication Year 2000-08-01,Volume 97,Issue #16,Page 9174-9179
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- CYTOKINE; DEFICIENCIES; INHIBITOR; DOMAIN; LIVER
- Publisher's Version
- https://doi.org/10.1073/pnas.160255197
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2000-08-01 12:00:00