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Molecular and Cellular Biology, June 2003, p. 3982-3989, Vol. 23, No. 11
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.11.3982-3989.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Frieder Schwenk,¹ Branko Zevnik,¹ Jens Brüning,² Mathias Röhl,² Antje Willuweit,¹ Anja Rode,¹ Thomas Hennek,¹ Gunther Kauselmann,¹ Rudolf Jaenisch,³ and Ralf Kühn^1*

Artemis Pharmaceuticals GmbH,¹ Klinik II und Poliklinik für Innere Medizin der Universität Köln and Center of Molecular Medicine, Cologne, Germany,² Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts³

Received 23 October 2002/ Returned for modification 25 November 2002/ Accepted 24 February 2003

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.

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* Corresponding author. Present address: GSF Research Center, Institute for Developmental Genetics, Ingolstaedter Landstrasse, 1, 85764 Neuherberg/Munich, Germany. Phone: 49 89 3187 3674. Fax: 49 89 3187 3099. E-mail: ralf.kuehn{at}gsf.de.

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Molecular and Cellular Biology, June 2003, p. 3982-3989, Vol. 23, No. 11
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.11.3982-3989.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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