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Molecular and Cellular Biology, March 2006, p. 2317-2326, Vol. 26, No. 6
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.6.2317-2326.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Generation and Characterization of dickkopf3 Mutant Mice

Ivan del Barco Barrantes,1,{dagger} Ana Montero-Pedrazuela,2 Ana Guadaño-Ferraz,2 Maria-Jesus Obregon,2 Raquel Martinez de Mena,2 Valérie Gailus-Durner,3 Helmut Fuchs,3 Tobias J. Franz,4 Svetoslav Kalaydjiev,4 Martina Klempt,5 Sabine Hölter,6 Birgit Rathkolb,5 Claudia Reinhard,7 Gabriella Morreale de Escobar,2 Juan Bernal,2 Dirk H. Busch,4 Wolfgang Wurst,6 Eckhard Wolf,5 Holger Schulz,7 Svetlana Shtrom,8 Erich Greiner,9 Martin Hrabé de Angelis,3 Heiner Westphal,8 and Christof Niehrs1*

Division of Molecular Embryology,1 Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany,9 Department of Molecular Endocrinology, Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Arturo Duperier 4, E-28029 Madrid, Spain,2 Institute of Experimental Genetics,3 Institute of Developmental Genetics,6 Institute for Inhalation Biology, GSF-National Research Center for Environment and Health, Ingolstaedter Landstr. 1, D-85758 Neuherberg, Germany,7 Institute for Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, Trogerstr. 9, D-81675 Munich, Germany,4 Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig Maximilian University of Munich, Feodor-Lynen-Strasse 25, 81377 Munich, Germany,5 National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892-27908

Received 6 October 2005/ Returned for modification 19 November 2005/ Accepted 21 December 2005

dickkopf (dkk) genes encode a small family of secreted Wnt antagonists, except for dkk3, which is divergent and whose function is poorly understood. Here, we describe the generation and characterization of dkk3 mutant mice. dkk3-deficient mice are viable and fertile. Phenotypic analysis shows no major alterations in organ morphology, physiology, and most clinical chemistry parameters. Since Dkk3 was proposed to function as thyroid hormone binding protein, we have analyzed deiodinase activities, as well as thyroid hormone levels. Mutant mice are euthyroid, and the data do not support a relationship of dkk3 with thyroid hormone metabolism. Altered phenotypes in dkk3 mutant mice were observed in the frequency of NK cells, immunoglobulin M, hemoglobin, and hematocrit levels, as well as lung ventilation. Furthermore, dkk3-deficient mice display hyperactivity.

* Corresponding author. Mailing address: Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. Phone: 49-6221-42-4690. Fax: 49-6221-42-4692. E-mail: niehrs{at}dkfz-Heidelberg.de.

{dagger} Present address: Cell Signalling Group, Centro Nacional de Investigaciones Oncologicas (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Molecular and Cellular Biology, March 2006, p. 2317-2326, Vol. 26, No. 6
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.6.2317-2326.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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