title: Inducible liver injury in the transgenic rat by expressing liver-specific suicide gene.
abstract: 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.
authors: Laboratory of Transplantation Immunology, Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan.
authors: Mikiko
authors: M
authors: Kawasaki
authors: Masayuki
authors: M
authors: Fujino
authors: Xiao-Kang
authors: XK
authors: Li
authors: Yusuke
authors: Y
authors: Kitazawa
authors: Naoko
authors: N
authors: Funeshima
authors: Ri-ichi
authors: R
authors: Takahashi
authors: Masatsugu
authors: M
authors: Ueda
authors: Takashi
authors: T
authors: Amano
authors: Yoji
authors: Y
authors: Hakamata
authors: Eiji
authors: E
authors: Kobayashi
mesh_terms: 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
chemical_list: D014764:Viral Proteins; D013937:Thymidine Kinase; D015774:Ganciclovir