Inducible liver injury in the transgenic rat by expressing liver-specific suicide gene.
Suicide gene expression in specific tissue of transgenic animals has been used for cell-specific ablation. To examine the influence of hepatocyte removal, we produced the herpes simplex virus thymidine kinase (HSVtk) transgenic rat, whose gene was regulated by an albumin enhancer promoter. The liver presence of HSVtk was demonstrated in one line of the transgenic rats. We injected ganciclovir (GCV, 50mg/kg) into the rat on alternate days. After 28 days of GCV administration, liver tissues, and blood of the rats were collected. The histological investigation revealed infiltration of T cells, macrophages, granulocytes/neutrophils, and hepatocyte cell death. The biochemistry analysis demonstrated elevated levels of AST, ALT, and total bilirubin in transgenic rat. In conclusion, the transgenic rat with expressed albumin-specific HSVtk developed experimental hepatitis with administration of GCV, and will be a useful model to facilitate the evaluation of drug effects for clinical control of liver disease.
Kawasaki
Mikiko
M
Laboratory of Transplantation Immunology, Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan.
Fujino
Masayuki
M
Li
Xiao-Kang
XK
Kitazawa
Yusuke
Y
Funeshima
Naoko
N
Takahashi
Ri-ichi
R
Ueda
Masatsugu
M
Amano
Takashi
T
Hakamata
Yoji
Y
Kobayashi
Eiji
E
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015774:Ganciclovir / Q000633:toxicity; D005786:Gene Expression Regulation; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D023421:Models, Animal; D051381:Rats / Q000235:genetics; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D014764:Viral Proteins; D013937:Thymidine Kinase; D015774:Ganciclovir