Transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) develop accumulations of macrophages, blindness, and a fatal syndrome of tissue damage

Cell. 1987 Nov 20;51(4):675-86. doi: 10.1016/0092-8674(87)90136-x.

Abstract

Transgenic mice carrying the murine granulocyte-macrophage colony stimulating factor (GM-CSF) gene expressed from a retroviral promoter exhibit elevated levels of GM-CSF in the serum, urine, peritoneal cavity, and eye. The eyes of transgenic mice are opaque, contain accumulations of macrophages, and develop retinal damage. Similarly, lesions containing macrophages develop in striated muscle. The mice also display an accumulation of large, often multinucleate, activated macrophages in the peritoneal and pleural cavities. The transgene is transcribed in peritoneal cells, as well as in eyes and infiltrated striated muscle. A high proportion of transgenic mice die with muscle wasting when aged 2-4 months, possibly because of macrophage activation resulting from the high levels of GM-CSF.

Publication types

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

MeSH terms

  • Animals
  • Cataract / etiology*
  • Cataract / pathology
  • Colony-Stimulating Factors / genetics
  • Colony-Stimulating Factors / toxicity*
  • Genes, Viral
  • Granulocytes
  • Macrophage Activation
  • Macrophages / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Moloney murine leukemia virus / genetics
  • Muscular Diseases / etiology*
  • Muscular Diseases / pathology
  • Organ Specificity
  • Peritoneal Cavity / pathology
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / toxicity*
  • Recombinant Proteins / toxicity*
  • Syndrome

Substances

  • Colony-Stimulating Factors
  • Recombinant Fusion Proteins
  • Recombinant Proteins