title: VelociMouse: fully ES cell-derived F0-generation mice obtained from the injection of ES cells into eight-cell-stage embryos.
abstract: With the completion of the human and mouse genome sequences and the development of high-throughput knockout mouse technologies, there is now a need for equally high-throughput methods for the production of mice for phenotypic studies. In response to this challenge, we recently developed a new method termed VelociMouse for the production of F0-generation mice that are fully derived from gene-targeted ES cells. In the version of the VelociMouse method described here, laser ablation of a portion of the zona pellucid (zp) of a normal eight-cell-stage embryo facilitates ES cell injection. Upon gestation in a surrogate mother, the injected embryos produce F0 mice that carry no detectable host embryo contribution (<0.1%). The fully ES cell-derived mice are normal, healthy, and fertile and exhibit 100% germline transmission for optimal breeding efficiency. The VelociMouse method accommodates both inbred or hybrid ES cells and either inbred or outbred eight-cell host embryos. Because the F0 mice produced are suitable for direct phenotyping studies, the VelociMouse method, coupled with high-throughput ES cell targeting technologies, such as VelociGene, offers an accelerated path to new drug target discovery and validation and a revolutionary approach to realize the full value of large-scale functional genomic efforts, such as the NIH Knockout Mouse Project ( 1 ) and the European Conditional Mouse Mutagenesis Project( 9 ).
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Dechiara
authors.forename: William T
authors.initials: WT
authors.lastname: Poueymirou
authors.forename: Wojtek
authors.initials: W
authors.lastname: Auerbach
authors.forename: David
authors.initials: D
authors.lastname: Frendewey
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D046149:Embryo Culture Techniques / Q000379:methods*; D004622:Embryo, Mammalian / Q000166:cytology*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000637:transplantation*; D005260:Female; D018390:Gene Targeting / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011247:Pregnancy