Enhanced GFAP expression in astrocytes of transgenic mice expressing the human brain-specific trypsinogen IV.
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.
Minn
A
A
Institut für Genetik, Lindenthal, Köln, Germany.
Schubert
M
M
Neiss
W F
WF
Müller-Hill
B
B
D016229:Amyloid beta-Peptides / Q000096:biosynthesis; D000818:Animals; D000918:Antibody Specificity; D001253:Astrocytes / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D014362:Trypsinogen / Q000096:biosynthesis*; D015854:Up-Regulation
D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D014362:Trypsinogen