RRC ID 2021
Author Kawasaki M, Fujino M, Li XK, Kitazawa Y, Funeshima N, Takahashi R, Ueda M, Amano T, Hakamata Y, Kobayashi E.
Title Inducible liver injury in the transgenic rat by expressing liver-specific suicide gene.
Journal Biochem. Biophys. Res. Commun.
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.
Volume 311(4)
Pages 920-8
Published 2003-11-28
PII S0006291X03021351
PMID 14623269
MeSH Animals Animals, Genetically Modified Apoptosis / drug effects Apoptosis / genetics Cells, Cultured Chemical and Drug Induced Liver Injury / genetics* Chemical and Drug Induced Liver Injury / metabolism* Dose-Response Relationship, Drug Ganciclovir / toxicity Gene Expression Regulation Genes, Transgenic, Suicide / genetics* Hepatocytes / drug effects* Hepatocytes / metabolism* Models, Animal Rats / genetics Simplexvirus / enzymology Thymidine Kinase / genetics* Thymidine Kinase / metabolism* Viral Proteins / genetics Viral Proteins / metabolism
IF 2.559
Times Cited 3
DNA material pCM-TK (RDB01692)