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.

Development of blastocyst complementation technology without contributions to gametes and the brain

“…In addition, female chimeras were considered to be theoretically unable to achieve germline transmission [2] because the karyotype of the ES cells used (EGR-G101) was XY. However, our female chimeras derived from XY ES cells achieved germline transmission in similar to previous study [15], as did the male and female chimeras derived from G-mESCs with Prdm14 and Otx2 genes obtained in our study. On the other hand, the G-mESCs without the Prdm14 and Otx2 genes successfully interrupted germline transmission from the male and female chimeras.…”

Live Birth in Sex-Reversed XY Mice Lacking the Nuclear Receptor Dax1

“…This work demonstrates that a minority of Dax1−/Y mice can produce live offspring without any assisted fertility treatment. It adds to the small number of reports of live-birth from sex-reversed XY mice (for example [16][17][18][19] ). There are reports of fertility in mutant XY sex-reversed wood lemmings (Myopus shisticolor) 20 , and XY-female horses 21 .…”