Expression of human alpha 1-acid glycoprotein genes in cultured cells and in transgenic mice.
The human genome contains three alpha 1-glycoprotein genes (AGP-A, AGP-B, and AGP-B') encoding for slightly different forms of the protein. The major component of human alpha 1-acid glycoprotein found in plasma is coded by AGP-A, which is expressed in liver and in hepatoma cell lines and is induced by inflammatory stimuli. We have studied the regulation of the cloned AGP-A gene by transfection into cell lines of hepatic and nonhepatic origin. Unlike any other liver-specific gene investigated so far, every AGP construct tested was expressed with comparable efficiency in hepatoma and HeLa cells. In contrast, identical constructs in transgenic mice are expressed in a tissue-specific manner and are regulated by acute-phase stimuli. Transgenic mice carrying the cluster of three AGP genes secrete the human protein in the serum, and the corresponding mRNA is mainly derived from the AGP-A gene. The mRNA is liver specific, and its concentration increases several fold following experimentally induced inflammation. Additional transgenic lines carrying only the AGP-A gene showed that sufficient information for tissue-specific and regulated expression is contained within a 6.6-kb segment comprising the whole coding region plus 1.2-kb 5'-flanking and 2-kb 3'-flanking DNA.
Dente
L
L
European Molecular Biology Laboratory, Heidelberg, RG.
Rüther
U
U
Tripodi
M
M
Wagner
E F
EF
Cortese
R
R
D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D005810:Multigene Family; D009961:Orosomucoid / Q000235:genetics*; D014158:Transcription, Genetic
D009961:Orosomucoid