A facile method for somatic, lifelong manipulation of multiple genes in the mouse liver

	A facile method for somatic, lifelong manipulation of multiple genes in the mouse liver
	Wangensteen, KJ; Wilber, A; Keng, VW; He, ZY; Matise, I; Wangensteen, L; Carson, CM; Chen, YX; Steer, CJ; McIvoir, RS
刊名	HEPATOLOGY
	2008
卷号	47 期号:5 页码:1714-1724
通讯作者	Ekker, SC (reprint author), Mayo Clin, Coll Med, Dept Biochem Mol Biol, 200 1st St SW,Guggenheim 1321A, Rochester, MN 55905 USA.,ekker.stephen@mayo.edu
英文摘要	Current techniques for the alteration of gene expression in the liver have a number of limitations, including the lack of stable somatic gene transfer and the technical challenges of germline transgenesis. Rapid and stable genetic engineering of the liver would allow systematic, in vivo testing of contributions by many genes to disease. After fumaryl acetoacetate hydrolase (Fah) gene transfer to hepatocytes, selective repopulation of the liver occurs in FAH-deficient mice. This genetic correction is readily mediated with transposons. Using this approach, we show that genes with biological utility can be linked to a selectable Fah transposon cassette. First, net conversion of Fah(-/-) liver tissue to transgenic tissue, and its outgrowth, was monitored by bioluminescence in vivo from a luciferase gene linked to the FAH gene. Second, coexpressed short hairpin RNAs (shRNAs) stably reduced target gene expression, indicating the potential for loss-of-function assays. Third, a mutant allele of human alpha 1-antitrypsin (hAAT) was linked to Fah and resulted in protein inclusions within hepatocytes, which are the histopathological hallmark of hAAT deficiency disorder. Finally, oncogenes linked to Fah resulted in transformation of transduced hepatocytes. Conclusion: Coexpression with FAH is an effective technique for lifelong expression of transgenes in adult hepatocytes with applicability to a wide variety of genetic studies in the liver.
学科主题	Gastroenterology & Hepatology
类目[WOS]	Gastroenterology & Hepatology
关键词[WOS]	TYROSINEMIA TYPE-I ; LONG-TERM EXPRESSION ; TRANSPOSON SYSTEM ; MURINE MODEL ; ALPHA(1)-ANTITRYPSIN DEFICIENCY ; HEPATOCELLULAR-CARCINOMA ; HEPATIC-DYSFUNCTION ; MAMMALIAN-CELLS ; HEMOPHILIC MICE ; VIVO CORRECTION
收录类别	SCI
语种	英语
WOS记录号	WOS:000255507500030
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1381]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Wangensteen, KJ,Wilber, A,Keng, VW,et al. A facile method for somatic, lifelong manipulation of multiple genes in the mouse liver[J]. HEPATOLOGY,2008,47(5):1714-1724.
APA	Wangensteen, KJ.,Wilber, A.,Keng, VW.,He, ZY.,Matise, I.,...&Ekker, SC.(2008).A facile method for somatic, lifelong manipulation of multiple genes in the mouse liver.HEPATOLOGY,47(5),1714-1724.
MLA	Wangensteen, KJ,et al."A facile method for somatic, lifelong manipulation of multiple genes in the mouse liver".HEPATOLOGY 47.5(2008):1714-1724.