Autoimmune manifestations in the transforming growth factor-beta 1 knockout mouse.
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.
Yaswen
L
L
Molecular and Medical Genetics Section, National Institute of Neurological Disorders and Stroke, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Kulkarni
A B
AB
Fredrickson
T
T
Mittleman
B
B
Schiffman
R
R
Payne
S
S
Longenecker
G
G
Mozes
E
E
Karlsson
S
S
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*
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D016212:Transforming Growth Factor beta