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Replacement of surgical vasectomy through the use of wild-type sterile hybrids

Abstract

For the production and rederivation of mouse strains, pseudopregnant female mice are used for embryo transfer and serve as surrogate mothers to support embryo development to term. Vasectomized males are commonly used to render pseudopregnancy in females, generated by surgical procedures associated with considerable pain and discomfort. Genetically modified mouse strains with a sterility phenotype provide a non-surgical replacement and represent an important application of the 3Rs (Replacement, Reduction, Refinement). However, the maintenance of such genetically modified mouse strains requires extensive breeding and genotyping procedures, which are regulated procedures under national legislation. As an alternative, we have explored the use of sterile male hybrids that result when two wild-type mouse subspecies, Mus musculus musculus and Mus musculus domesticus, interbreed. We find the male STUSB6F1 hybrid, resulting from the mating of female STUS/Fore with male C57BL/6J, ideally suited and demonstrate that its performance for the production of oviduct and uterine transfer recipients is indistinguishable when compared to surgically vasectomized mice. The use of these sterile hybrids avoids the necessity for surgical procedures or the breeding of sterile genetically modified lines and can be generated by the simple mating of two wild-type laboratory strains—a non-regulated procedure. Furthermore, in contrast with the breeding of genetically sterile mice, all male offspring are sterile and suitable for the generation of pseudopregnancy, allowing their efficient production with minimal breeding pairs.

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Fig. 1: Confirmation of the infertility of STUSB6F1.
Fig. 2: Comparison of litter production.

Data availability

All data generated or analyzed during this study are included in this published article (and its Supporting Information files). The STUS/Fore strain is available on request. Source data are provided with this paper.

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Acknowledgements

This work was supported by a Wellcome Trust Core Award Grant (203141/Z/16/Z) and a National Centre for the Replacement, Refinement and Reduction of Animals in Research project grant (NC/R001014/1).

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C.P., D.B. and S.A. performed the animal work. D.M. performed the cytological analysis of spermatocytes. S.A. and B.D. designed the study. S.A. and A.B. analyzed the data, and B.D. wrote the manuscript.

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Correspondence to Benjamin Davies.

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Raw data used for the preparation of Fig. 2

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Preece, C., Alghadban, S., Bouchareb, A. et al. Replacement of surgical vasectomy through the use of wild-type sterile hybrids. Lab Anim 50, 49–52 (2021). https://doi.org/10.1038/s41684-020-00692-w

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