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Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease

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Abstract

Transforming growth factor-β1 (TGF-β1) is a multifunctional growth factor that has profound regulatory effects on many developmental and physiological processes. Disruption of the TGF-β1 gene by homologous recombination in murine embryonic stem cells enables mice to be generated that carry the disrupted allele. Animals homozygous for the mutated TGF-β1 allele show no gross developmental abnormalities, but about 20 days after birth they succumb to a wasting syndrome accompanied by a multifocal, mixed inflammatory cell response and tissue necrosis, leading to organ failure and death. TGF-β1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions.

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Authors and Affiliations

  1. Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, 45267–0524, USA

    Marcia M. Shull, Ilona Ormsby, Sharon Pawlowski, Ronald J. Diebold, Moying Yin, Ruth Allen, Charles Sidman, Gabriele Proetzel & Thomas Doetschman

  2. Division of Comparative Pathology, Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, 45267–0524, USA

    Ann B. Kier, Dawn Calvin & Nikki Annunziata

Authors
  1. Marcia M. Shull
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  2. Ilona Ormsby
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  3. Ann B. Kier
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  4. Sharon Pawlowski
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  7. Ruth Allen
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  12. Thomas Doetschman
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Shull, M., Ormsby, I., Kier, A. et al. Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease. Nature 359, 693–699 (1992). https://doi.org/10.1038/359693a0

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  • DOI: https://doi.org/10.1038/359693a0

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