Hepatic gene transfer in animals using retroviruses containing the promoter from the gene for phosphoenolpyruvate carboxykinase.
Two methods are described for directing the expression of genes to the livers of animals using retroviral vectors containing the predominantly liver-specific promoter from the gene for phosphoenolpyruvate carboxykinase (PEPCK)-linked to the structural gene for either amino 3'-glycosyl phosphotransferase (neo) or bovine growth hormone (bGH). Replication-incompetent retrovirus was used to infect the livers of fetal rats by intraperitoneal injection of animals in utero or to infect adult rats by direct injection into the portal vein after partial hepatectomy. The proviruses were integrated into the hepatic DNA, and the chimeric genes were expressed from the PEPCK promoter for as long as 8 months after infection. The expression of the PEPCK-bGH gene was regulated by diet and hormones in a manner similar to the regulation of the endogenous PEPCK gene in the liver. The potential of this method for targeting genes to the liver is discussed.
Hatzoglou
M
M
Pew Center for Molecular Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
Lamers
W
W
Bosch
F
F
Wynshaw-Boris
A
A
Clapp
D W
DW
Hanson
R W
RW
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002678:Chimera; D015342:DNA Probes; D003907:Dexamethasone / Q000494:pharmacology; D005784:Gene Amplification; D005796:Genes; D005822:Genetic Vectors; D013006:Growth Hormone / Q000097:blood / Q000235:genetics; D019868:Kanamycin Kinase; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics*; D010770:Phosphotransferases / Q000235:genetics; D011401:Promoter Regions, Genetic; D051381:Rats; D015183:Restriction Mapping; D012190:Retroviridae / Q000235:genetics*; D014162:Transfection
D015342:DNA Probes; D015345:Oligonucleotide Probes; D003907:Dexamethasone; D013006:Growth Hormone; D010770:Phosphotransferases; D019868:Kanamycin Kinase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)