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Molecular and Cellular Biology, January 2006, p. 199-208, Vol. 26, No. 1
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.1.199-208.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Kaiso-Deficient Mice Show Resistance to Intestinal Cancer{dagger}

Anna Prokhortchouk,1,{ddagger} Owen Sansom,2,§ Jim Selfridge,1 Isabel M. Caballero,3 Sergey Salozhin,4 Dana Aithozhina,4 Leandro Cerchietti,5 Fan Guo Meng,5 Leonard H. Augenlicht,6 John M. Mariadason,6 Brian Hendrich,3 Ari Melnick,5 Egor Prokhortchouk,4 Alan Clarke,2 and Adrian Bird1*

Wellcome Trust Centre for Cell Biology, The King's Buildings, Edinburgh University, Edinburgh, United Kingdom,1 Cardiff School of Biosciences, Cardiff University, Cardiff, Wales, United Kingdom,2 Center "Bioengineering," Russian Academy of Sciences, Moscow, Russia,4 Department of Developmental and Molecular Biology and Medical Oncology, Albert Einstein College of Medicine, Bronx, New York 10461,5 Institute for Stem Cell Research, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3JQ, United Kingdom,3 Montefiore Medical Center, Albert Einstein Cancer Center, Bronx, New York 104676

Received 27 May 2005/ Returned for modification 9 July 2005/ Accepted 10 October 2005

Kaiso is a BTB domain protein that associates with the signaling molecule p120-catenin and binds to the methylated sequence mCGmCG or the nonmethylated sequence CTGCNA to modulate transcription. In Xenopus laevis, xKaiso deficiency leads to embryonic death accompanied by premature gene activation in blastulae and upregulation of the xWnt11 gene. Kaiso has also been proposed to play an essential role in mammalian synapse-specific transcription. We disrupted the Kaiso gene in mice to assess its role in mammalian development. Kaiso-null mice were viable and fertile, with no detectable abnormalities of development or gene expression. However, when crossed with tumor-susceptible ApcMin/+ mice, Kaiso-null mice showed a delayed onset of intestinal tumorigenesis. Kaiso was found to be upregulated in murine intestinal tumors and is expressed in human colon cancers. Our data suggest that Kaiso plays a role in intestinal cancer and may therefore represent a potential target for therapeutic intervention.

* Corresponding author. Mailing address: Wellcome Trust Centre for Cell Biology, The King's Buildings, Edinburgh University, Edinburgh EH9 3JR, United Kingdom. Phone: 0131-650-5670. Fax: 0131-650-5379. E-mail: a.bird{at}ed.ac.uk.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: Center "Bioengineering," Russian Academy of Sciences, Moscow, Russia.

§ Present address: CR-UK Beatson Institute for Cancer Research, Glasgow G61 1BD, United Kingdom.

Molecular and Cellular Biology, January 2006, p. 199-208, Vol. 26, No. 1
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.1.199-208.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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