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Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease.

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional growth factor that has profound regulatory effects on many developmental and physiological processes. Disruption of the TGF-beta 1 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-beta 1 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-beta 1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions.

Pubmed ID: 1436033

Authors

  • Shull MM
  • Ormsby I
  • Kier AB
  • Pawlowski S
  • Diebold RJ
  • Yin M
  • Allen R
  • Sidman C
  • Proetzel G
  • Calvin D

Journal

Nature

Publication Data

October 22, 1992

Associated Grants

  • Agency: NICHD NIH HHS, Id: R01 HD026471

Mesh Terms

  • Animals
  • Base Sequence
  • Cytokines
  • Gene Expression
  • Genes
  • Homozygote
  • Inflammation
  • Leukocyte Count
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Necrosis
  • Oligodeoxyribonucleotides
  • Polymerase Chain Reaction
  • RNA, Messenger
  • Restriction Mapping
  • Transforming Growth Factor beta