title: Generation of fertile and fecund F0 XY female mice from XY ES cells.
abstract: Known examples of male to female sex reversal in mice are caused by either strain incompatibilities or mutations in genes required for male sex determination. The resultant XY females are often sterile or exhibit very poor fertility. We describe here embryonic stem (ES) cell growth conditions that promote the production of healthy, anatomically normal fertile and fecund female F0 generation mice completely derived from gene-targeted XY male ES cells. The sex reversal is a transient trait that is not transmitted to the F1 progeny. Growth media with low osmolality and reduced sodium bicarbonate, maintained throughout the gene targeting process, enhance the yield of XY females. As a practical application of the induced sex reversal, we demonstrate the generation of homozygous mutant mice ready for phenotypic studies by the breeding of F0 XY females with their isogenic XY male clonal siblings, thereby eliminating one generation of breeding and the associated costs.
authors.affiliation: Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA.
authors.forename: Junko
authors.initials: J
authors.lastname: Kuno
authors.forename: William T
authors.initials: WT
authors.lastname: Poueymirou
authors.forename: Guochun
authors.initials: G
authors.lastname: Gong
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Siao
authors.forename: Georgia
authors.initials: G
authors.lastname: Clarke
authors.forename: Lakeisha
authors.initials: L
authors.lastname: Esau
authors.forename: Nada
authors.initials: N
authors.lastname: Kojak
authors.forename: Julita
authors.initials: J
authors.lastname: Posca
authors.forename: Amanda
authors.initials: A
authors.lastname: Atanasio
authors.forename: John
authors.initials: J
authors.lastname: Strein
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.forename: Ka-Man Venus
authors.initials: KM
authors.lastname: Lai
authors.forename: Thomas M
authors.initials: TM
authors.lastname: DeChiara
authors.forename: David
authors.initials: D
authors.lastname: Frendewey
authors.forename: Wojtek
authors.initials: W
authors.lastname: Auerbach
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
mesh_terms: D000818:Animals; D012734:Disorders of Sex Development / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology; D005260:Female; D005298:Fertility / Q000235:genetics*; D018390:Gene Targeting; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics*; D008297:Male; D051379:Mice; D008845:Microinjections; D009154:Mutation; D019849:Sex Determination Processes
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