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

Marcia M. Shull, Ilona Ormsby, Ann B. Kier, Sharon Pawlowski, Ronald J. Diebold, Moying Yin, Ruth Allen, Charles Sidman, Gabriele Proetzel, Dawn Calvin, Nikki Annunziata, Thomas C Doetschman

Research output: Contribution to journalArticle

2382 Citations (Scopus)

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-deflcient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions.

Original languageEnglish (US)
Pages (from-to)693-699
Number of pages7
JournalNature
Volume359
Issue number6397
StatePublished - Oct 22 1992
Externally publishedYes

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Transforming Growth Factors
Genes
Alleles
Physiological Phenomena
Wasting Syndrome
Homologous Recombination
Immune System Diseases
Graft Rejection
Autoimmune Diseases
Intercellular Signaling Peptides and Proteins
Necrosis
Parturition
Transplants

ASJC Scopus subject areas

  • General

Cite this

Shull, M. M., Ormsby, I., Kier, A. B., Pawlowski, S., Diebold, R. J., Yin, M., ... Doetschman, T. C. (1992). Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease. Nature, 359(6397), 693-699.

Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease. / Shull, Marcia M.; Ormsby, Ilona; Kier, Ann B.; Pawlowski, Sharon; Diebold, Ronald J.; Yin, Moying; Allen, Ruth; Sidman, Charles; Proetzel, Gabriele; Calvin, Dawn; Annunziata, Nikki; Doetschman, Thomas C.

In: Nature, Vol. 359, No. 6397, 22.10.1992, p. 693-699.

Research output: Contribution to journalArticle

Shull, MM, Ormsby, I, Kier, AB, Pawlowski, S, Diebold, RJ, Yin, M, Allen, R, Sidman, C, Proetzel, G, Calvin, D, Annunziata, N & Doetschman, TC 1992, 'Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease', Nature, vol. 359, no. 6397, pp. 693-699.
Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ, Yin M et al. Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease. Nature. 1992 Oct 22;359(6397):693-699.
Shull, Marcia M. ; Ormsby, Ilona ; Kier, Ann B. ; Pawlowski, Sharon ; Diebold, Ronald J. ; Yin, Moying ; Allen, Ruth ; Sidman, Charles ; Proetzel, Gabriele ; Calvin, Dawn ; Annunziata, Nikki ; Doetschman, Thomas C. / Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease. In: Nature. 1992 ; Vol. 359, No. 6397. pp. 693-699.
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