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

      Nature

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

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          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.

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          Author and article information

          Journal
          10.1038/359693a0
          3889166
          1436033

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