Generation and Characterization of dickkopf3 Mutant Mice

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.

We thank Sonia Pinho, Dana Hoppe, Socorro Duran, Maria Jesus Presas, Elena Fernandez-Duran, Maria Asuncion Navarro, and Marina Sanz-Sancristobal for excellent technical assistance and the screeners of the German Mouse Clinic for phenotypical analysis of the mice.

This work was supported by the DFG (SFB 488 A1), grants SAF2001-2243 and FIS RCMN 03/08 (M.-J.O.), BFI2001-2412 and BFU2004-05944 (A.G-F.), NGFN 01GR0430, and 01GR0434, 01GR0458, and 01GR0103 (GMC).