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. Research Abstract Details 

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A facile method for somatic, lifelong manipulation of multiple genes in the mouse liver. Abstract Text:

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 alpha1-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. (HEPATOLOGY 2008;47:1714-1724.).

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A facile method for somatic, lifelong manipulation of multiple genes in the mouse liver. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Hepatology (Baltimore, Md.)

VOLUME: 47

Page Numbers: 1714-24

Journal Abbreviation: Hepatology

ISSN: 1527-3350

DAY: 1

MONTH: May

YEAR: 2008

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

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LANGUAGE: eng

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Grant and Affiliation Information for A facile method for somatic, lifelong manipulation of multiple genes in the mouse liver.

AFFILIATION: The Arnold and Mabel Beckman Center for Transposon Research, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN.

Country: United States

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MEDLINETA: Hepatology

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