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Breaking the Species Barrier: Derivation of Germline-Competent Embryonic Stem Cells from Mus spretus x C57BL/6 Hybrids

^a Molecular Genetics of the Mouse, Department for Molecular Biomedical Research, Ghent University and Flanders Interuniversity Institute for Biotechnology, Ghent, Belgium;
^b Thromb-X N.V., Center for Molecular and Vascular Biology, Catholic University of Leuven, Leuven, Belgium

Key Words. Embryonic stem cell • Mus spretus • Germline transmission • TNF

Correspondence: Claude Libert, Ph.D., Department of Molecular and Biomedical Research, University of Ghent/VIB, Technologiepark 927, B-9052 Zwijnaarde, Belgium. Telephone: 00-32-9-331-3700; Fax: 00-32-9-331-3609; e-mail: Claude.Libert{at}dmbr.UGent.be

Embryonic stem (ES) cells, which can differentiate into almost all types of cells, have been derived from the house mouse Mus musculus, rat, rabbit, humans, and other species. Transmission of the genotype to the offspring of chimeras has been achieved only with M. musculus ES cells, limiting targeted mutagenesis using ES cells to this species. Mus spretus, which exhibits many genetic polymorphisms with M. musculus, displays dominant resistance to cancer and inflammation, making derived inbred strains very useful in positional cloning and interspecies mapping. We show here for the first time the derivation of ES cells from hybrid blastocysts, obtained by the mating of two different species, namely Mus musculus and Mus spretus, and their use for the generation of chimeric mice that transmit the Mus spretus genotype and phenotype to the offspring. These hybrid ES cells allow the genetic manipulation of Mus spretus, as an alternative to Mus musculus.