Enhanced GFAP expression in astrocytes of transgenic mice expressing the human brain-specific trypsinogen IV

Glia. 1998 Apr;22(4):338-47. doi: 10.1002/(sici)1098-1136(199804)22:4<338::aid-glia3>3.0.co;2-#.


We recently identified a cDNA encoding a human brain specific trypsinogen (trypsinogen IV). In order to test whether trypsinogen IV is involved in CNS diseases of, or injury response in, mammalian brain, a mouse model was developed in which the human trypsinogen IV was expressed specifically in neurons. Immunocytochemical analysis of the brains of transgenic mice revealed a striking enhancement of glial fibrillar acidic protein (GFAP) expression in astrocytes. This remarkable astrocytic reaction was detected in the brains of mice as young as 2 months and did not diminish in the older animals we tested. However, we did not find gross evidence for neurodegeneration, nor for reactive microglial cells. The long-term survival of these animals should provide a model with which to study the mechanism of nerve-astroglia interactions. In addition, the possible participation of trypsin IV in the metabolism of the Alzheimer precursor protein (APP) was investigated by immunostaining brains from transgenic mice with beta-amyloid (betaA4) antibodies. Immunocytochemical staining of brains from one year old transgenic mice revealed an intense intracellular betaA4-like signal in neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / biosynthesis
  • Animals
  • Antibody Specificity
  • Astrocytes / metabolism*
  • Blotting, Northern
  • Blotting, Western
  • Brain / enzymology*
  • Female
  • Glial Fibrillary Acidic Protein / biosynthesis*
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Transgenic
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • Trypsinogen / biosynthesis*
  • Up-Regulation


  • Amyloid beta-Peptides
  • Glial Fibrillary Acidic Protein
  • RNA, Messenger
  • Trypsinogen