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Am J Physiol Gastrointest Liver Physiol 292: G996-G1001, 2007. First published December 14, 2006; doi:10.1152/ajpgi.00493.2006
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LIVER AND BILIARY TRACT

Delayed liver regeneration in mice lacking liver serum response factor

M. Ujue Latasa,1 Dominique Couton,1 Claude Charvet,1 Aurélie Lafanechère,1 Jacques-Emmanuel Guidotti,1 Zhenlin Li,2 David Tuil,1 Dominique Daegelen,1 Claudia Mitchell,1 and Hélène Gilgenkrantz1

1Institut Cochin, Genetic and Development Department U.567, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche 8104, Université René Descartes, Paris; and 2CNRS UMR 7079, Université Pierre et Marie Curie, Paris, France

Submitted 23 October 2006 ; accepted in final form 8 December 2006

Various immediate early genes (IEGs) upregulated during the early process of liver regeneration are transcriptional targets of the serum response factor (SRF). We show here that the expression of SRF is rapidly induced in rodent liver after partial hepatectomy. Because the inactivation of the SRF gene in mice is embryonic lethal, the in vivo role of SRF in liver regeneration after partial hepatectomy was analyzed in mutant mice conditionally deleted for SRF in the liver. We demonstrate that SRF is not an essential factor for liver ontogenesis. However, adult mutant mice show impaired liver regeneration after partial hepatectomy, associated with a blunted upregulation of various SRF target IEGs. In conclusion, our work suggests that SRF is an early response transcription factor that may contribute to the initial phases of liver regeneration through its activation of IEGs.

conditional inactivation; hepatocyte; cell cycle



Address for reprint requests and other correspondence: H. Gilgenkrantz, Institut Cochin, Genetics and Development Dept., 24 Rue du Fbg St. Jacques, 75014 Paris, France (e-mail: gilgenkrantz{at}cochin.inserm.fr)




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