A Mouse Model of Inducible Liver Injury Caused by Tet-On Regulated   Urokinase for Studies of Hepatocyte Transplantation

doi:10.2353/ajpath.2009.090349

CORC > 北京大学 > 生命科学学院

	A Mouse Model of Inducible Liver Injury Caused by Tet-On Regulated Urokinase for Studies of Hepatocyte Transplantation
	Song, Xijun ; Guo, Yushan ; Duo, Shuguang ; Che, Jie ; Wu, Chen ; Ochiya, Takahiro ; Ding, Mingxiao ; Deng, Hongkui
刊名	american journal of pathology
	2009
关键词	PLASMINOGEN-ACTIVATOR TRANSGENE GENE-TRANSFER GROWTH-FACTOR RAT-LIVER IN-VIVO ADENOVIRUS MICE EXPRESSION REPOPULATION CELLS
DOI	10.2353/ajpath.2009.090349
英文摘要	Mouse models of liver injury provide useful tools for studying hepatocyte engraftment and proliferation. A representative model of liver injury is the albumin-urokinase (Alb-uPA) transgenic model, but neonatal lethality hampers its widespread application. To overcome this problem, we generated a transgenic mouse in which transcription of the reverse tetracycline transactivator was (rtTA) driven by the mouse albumin promoter, and backcrossed the rtTA mice onto severe combined immunodeficient (SCID)/bg mice to generate immunodeficient rtTA/SCID mice. We then produced recombinant adenoviruses Ad.TRE-uPA, in which the urokinase was located downstream of the tetracycline response element (TRE). The rtTA/SCID mouse hepatocytes were then infected with Ad.TRE-uPA to establish an inducible liver injury mouse model. in the presence of doxycycline, uPA was exclusively expressed in endogenous hepatocytes and caused extensive liver injury. Enhanced green fluorescent protein-labeled mouse hepatocytes selectively repopulated the rtTA/SCID mouse liver and replaced over 80% of the recipient liver mass after repeated administration of Ad.TRE-uPA. Compared with the original uPA mice, rtTA/SCID mice did not exhibit problems regarding breeding efficiency, and the time window for transplantation was flexible. In addition, we could control the extent of liver injury to facilitate transplantation surgery by regulating the dose of Ad.TRE-uPA. Our inducible mouse model will be convenient for studies of hepatocyte transplantation and hepatic regeneration, and this system will facilitate screening for potential genetic factors critical for engraftment and proliferation of hepatocytes in vivo. (Am J Pathol 2009, 175:1975-1983 DOI: 10.2353/ajpath.2009.090349); Pathology; SCI(E); PubMed; 9; ARTICLE; 5; 1975-1983; 175
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/344796]
专题	生命科学学院
推荐引用方式 GB/T 7714	Song, Xijun,Guo, Yushan,Duo, Shuguang,et al. A Mouse Model of Inducible Liver Injury Caused by Tet-On Regulated Urokinase for Studies of Hepatocyte Transplantation[J]. american journal of pathology,2009.
APA	Song, Xijun.,Guo, Yushan.,Duo, Shuguang.,Che, Jie.,Wu, Chen.,...&Deng, Hongkui.(2009).A Mouse Model of Inducible Liver Injury Caused by Tet-On Regulated Urokinase for Studies of Hepatocyte Transplantation.american journal of pathology.
MLA	Song, Xijun,et al."A Mouse Model of Inducible Liver Injury Caused by Tet-On Regulated Urokinase for Studies of Hepatocyte Transplantation".american journal of pathology (2009).