Hybrid Embryonic Stem Cell-Derived Tetraploid Mice Show Apparently Normal Morphological, Physiological, and Neurological Characteristics

Abstract

ES cell-tetraploid (ES) mice are completely derived from embryonic stem cells and can be obtained at high efficiency upon injection of hybrid ES cells into tetraploid blastocysts. This method allows the immediate generation of targeted mouse mutants from genetically modified ES cell clones, in contrast to the standard protocol, which involves the production of chimeras and several breeding steps. To provide a baseline for the analysis of ES mouse mutants, we performed a phenotypic characterization of wild-type B6129S6F₁ ES mice in relation to controls of the same age, sex, and genotype raised from normal matings. The comparison of 90 morphological, physiological, and behavioral parameters revealed elevated body weight and hematocrit as the only major difference of ES mice, which exhibited an otherwise normal phenotype. We further demonstrate that ES mouse mutants can be produced from mutant hybrid ES cells and analyzed within a period of only 4 months. Thus, ES mouse technology is a valid research tool for rapidly elucidating gene function in vivo.

ACKNOWLEDGMENTS

We thank I. Falkner, A. Hortz, D. Schulz, and D. Thiel for excellent technical assistance, J. Lühler for comments, and G. Stott and L. Jackson-Grusby for critically reading the manuscript.

This work was supported by Artemis Pharmaceuticals GmbH and the German Ministry for Education and Science (BMBF, grants 0311956 and ZMMKTV2).

F. Schwenk and B. Zevnik contributed equally to this work.