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.
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February 15, 1996
Autoimmune manifestations in the transforming growth factor-beta 1 knockout mouse
L Yaswen,
L Yaswen
Molecular and Medical Genetics Section, National Institute of Neurological Disorders and Stroke, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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AB Kulkarni,
AB Kulkarni
Molecular and Medical Genetics Section, National Institute of Neurological Disorders and Stroke, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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T Fredrickson,
T Fredrickson
Molecular and Medical Genetics Section, National Institute of Neurological Disorders and Stroke, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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B Mittleman,
B Mittleman
Molecular and Medical Genetics Section, National Institute of Neurological Disorders and Stroke, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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R Schiffman,
R Schiffman
Molecular and Medical Genetics Section, National Institute of Neurological Disorders and Stroke, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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S Payne,
S Payne
Molecular and Medical Genetics Section, National Institute of Neurological Disorders and Stroke, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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G Longenecker,
G Longenecker
Molecular and Medical Genetics Section, National Institute of Neurological Disorders and Stroke, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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E Mozes,
E Mozes
Molecular and Medical Genetics Section, National Institute of Neurological Disorders and Stroke, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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S Karlsson
S Karlsson
Molecular and Medical Genetics Section, National Institute of Neurological Disorders and Stroke, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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Blood (1996) 87 (4): 1439–1445.
Citation
L Yaswen, AB Kulkarni, T Fredrickson, B Mittleman, R Schiffman, S Payne, G Longenecker, E Mozes, S Karlsson; Autoimmune manifestations in the transforming growth factor-beta 1 knockout mouse. Blood 1996; 87 (4): 1439–1445. doi: https://doi.org/10.1182/blood.V87.4.1439.bloodjournal8741439
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February 15 1996
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