Generation of a mouse expressing a conditional knockout of the hepatocyte growth factor gene: demonstration of impaired liver regeneration

DNA and Cell Biology
Daniel PhaneufJames M Wilson

Abstract

Hepatocyte growth/scatter factor (HGF/SF) is a pleiotropic cytokine originally identified as a potent mitogen for rat hepatocytes. Two HGF/SF knockout mouse models have been reported, both of which exhibit developmental abnormalities causing embryonic lethality. To circumvent this limitation, we created a mouse conditionally deficient in liver expression of HGF/SF to specifically investigate the role of this mitogen in the process of adult liver regeneration. Gene targeting technology was used to generate a mouse with loxP sites flanking exon 5 of the HGF/SF gene (ex5-flox). In the absence of cre recombinase activity, mice homozygous for ex5-flox were indistinguishable from wild-type littermates. To ablate HGF/SF gene expression in vitro, primary hepatocytes established from homozygous HGF(ex5-flox) mice were infected with a recombinant adenoviral vector coding for cre recombinase (AdCre1). PCR analyses of genomic DNA demonstrated greater than 90% ablation of the ex5-floxed gene sequence. In vivo, HGF(ex.5-flox) mice were administered AdCre1 vector and the ablation of the HGF gene confirmed by Southern blot analysis. To induce liver regeneration, mice were injected with the hepatotoxin carbon tetrachloride. The regenerative cap...Continue Reading

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Citations

Nov 5, 2010·World Journal of Gastroenterology : WJG·Aránzazu Sánchez, Isabel Fabregat
Apr 18, 2012·Journal of Pineal Research·Almudena LalienaMaría J Tuñón
Apr 4, 2008·The American Journal of Pathology·Gaelle del CastilloAránzazu Sánchez
Jul 7, 2009·American Journal of Human Genetics·Julie M SchultzRobert J Morell
Dec 7, 2007·Biochemical and Biophysical Research Communications·Yohsuke MatsumotoEiichi Gohda
Aug 3, 2007·Nephron. Experimental Nephrology·Izaya NakayaShuichi Kaneko
Jan 27, 2006·World Journal of Gastroenterology : WJG·Toshiyuki OtsukaMasatomo Mori
May 27, 2015·World Journal of Biological Chemistry·Yu-Wen Zhang
Nov 5, 2014·Biomedicines·Ognoon MungunsukhRegina M Day
Apr 28, 2021·The Journal of Clinical Investigation·Sonakshi BhattacharjeeRobert F Schwabe

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