Targeted Disruption of the Mouse Transforming Growth Factor-Beta 1 Gene Results in Multifocal Inflammatory Disease

Nature. 1992 Oct 22;359(6397):693-9. doi: 10.1038/359693a0.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • Cytokines
  • Oligodeoxyribonucleotides
  • RNA, Messenger
  • Transforming Growth Factor beta