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. |
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