Targeted retroviral gene transfer into the rat biliary tract.
The ability to induce proliferation by temporary duct ligation suggested an hypothesis that retrovirus-mediated gene transfer into cells of the biliary tract could be accomplished. The time course of histologic changes, incorporation of 3H-thymidine and immunofluorescent staining with a monoclonal antibody to cytokeratin-19 (a marker for differentiated bile ducts) was studied in male Fischer F344 rats. A recombinant Gibbon ape leukemia virus (GALV), containing a gene encoding Escherichia coli beta-galactosidase was next introduced into 24 hr obstructed bile ducts. Gene transfer was maximal when virus was exposed to the obstructed duct for 12 hr (approximately 0.1%). The majority of X-gal positive cells were in cytokeratin-19 negative peribiliary tissues, which had the appearance of newly forming bile ducts. The data suggest that cells targeted by retroviral infection of the obstructed rat bile duct may be a precursor of mature, fully differentiated biliary epithelium.
Cabrera
J A
JA
University of Michigan Medical School, USA.
Wilson
J M
JM
Raper
S E
SE
D000818:Animals; D001652:Bile Ducts / Q000737:chemistry / Q000166:cytology* / Q000601:surgery; D002453:Cell Cycle; D002455:Cell Division; D002779:Cholestasis; D004847:Epithelial Cells; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D018014:Gene Transfer Techniques; D007633:Keratins / Q000032:analysis; D017989:Leukemia Virus, Gibbon Ape / Q000235:genetics*; D008026:Ligation; D008099:Liver / Q000737:chemistry / Q000166:cytology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D007633:Keratins; D001616:beta-Galactosidase