title: Autoimmune manifestations in the transforming growth factor-beta 1 knockout mouse.
abstract: Targeted disruption of the transforming growth factor-beta 1 (TGF-beta 1) gene in mice results in the development of a massive multifocal inflammatory disease in many tissues. Because no detectable pathogen was identified, we examined whether autoimmune mechanisms played a role in initiating or maintaining the inflammatory disease. The serum of TGF-beta 1 knockout mice contained elevated titers of antibodies to nuclear antigens (ssDNA, dsDNA, Sm, and RNP) as well as reactivity against the 16/6 idiotype (16/6 Id). In addition, Ig deposits were detected in renal glomeruli of TGF- beta 1 knockout mice. Transplantation of TGF-beta 1 knockout hematopoietic cells into normal irradiated recipients resulted in a similar profile of autoantibody production as well as in the induction of inflammatory lesions. Our results describe autoimmune activity that ensues when the TGF-beta 1 cytokine is absent.
authors.affiliation: Molecular and Medical Genetics Section, National Institute of Neurological Disorders and Stroke, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: L
authors.initials: L
authors.lastname: Yaswen
authors.forename: A B
authors.initials: AB
authors.lastname: Kulkarni
authors.forename: T
authors.initials: T
authors.lastname: Fredrickson
authors.forename: B
authors.initials: B
authors.lastname: Mittleman
authors.forename: R
authors.initials: R
authors.lastname: Schiffman
authors.forename: S
authors.initials: S
authors.lastname: Payne
authors.forename: G
authors.initials: G
authors.lastname: Longenecker
authors.forename: E
authors.initials: E
authors.lastname: Mozes
authors.forename: S
authors.initials: S
authors.lastname: Karlsson
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D007105:Immune Complex Diseases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D016212:Transforming Growth Factor beta