Generation and Characterization of dickkopf3 Mutant Mice

Author:

del Barco Barrantes Ivan1,Montero-Pedrazuela Ana2,Guadaño-Ferraz Ana2,Obregon Maria-Jesus2,Martinez de Mena Raquel2,Gailus-Durner Valérie3,Fuchs Helmut3,Franz Tobias J.4,Kalaydjiev Svetoslav4,Klempt Martina5,Hölter Sabine6,Rathkolb Birgit5,Reinhard Claudia7,Morreale de Escobar Gabriella2,Bernal Juan2,Busch Dirk H.4,Wurst Wolfgang6,Wolf Eckhard5,Schulz Holger7,Shtrom Svetlana8,Greiner Erich9,Hrabé de Angelis Martin3,Westphal Heiner8,Niehrs Christof1

Affiliation:

1. Division of Molecular Embryology

2. 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

3. Institute of Experimental Genetics

4. Institute for Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, Trogerstr. 9, D-81675 Munich, Germany

5. Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig Maximilian University of Munich, Feodor-Lynen-Strasse 25, 81377 Munich, Germany

6. Institute of Developmental Genetics

7. Institute for Inhalation Biology, GSF-National Research Center for Environment and Health, Ingolstaedter Landstr. 1, D-85758 Neuherberg, Germany

8. National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892-2790

9. Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany

Abstract

ABSTRACT 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.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

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