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A Y-encoded subunit of the translation initiation factor Eif2 is essential for mouse spermatogenesis

Nature Genetics volume 29, pages 49–53 (2001)Cite this article

Abstract

In mouse and man, deletions of specific regions of the Y chromosome have been linked to early failure of spermatogenesis and consequent sterility; the Y chromosomal gene(s) with this essential early role in spermatogenesis have not been identified. The partial deletion of the mouse Y short arm (the Sxrb deletion) that occurred when Tp(Y)1CtSxr-b (hereafter Sxrb) arose from Tp(Y)1CTSxr-b (hereafter Sxra) defines Spy, a Y chromosomal factor essential for normal spermatogonial proliferation1,2,3. Molecular analysis has identified six genes that lie within the deletion: Ube1y1 (refs. 4,5), Smcy6, Uty7, Usp9y (also known as Dffry)8, Eif2s3y (also known as Eif-2γy)9 and Dby10; all have closely similar X-encoded homologs. Of the Y-encoded genes, Ube1y1 and Dby have been considered strong candidates for mouse Spy function4,5,10,11, whereas Smcy has been effectively ruled out as a candidate12. There is no Ube1y1 homolog in man, and DBY, either alone or in conjunction with USP9Y, is the favored candidate for an early spermatogenic role10,13,14,15. Here we show that introduction of Ube1y1 and Dby as transgenes into Sxrb-deletion mice fails to overcome the spermatogenic block. However, the introduction of Eif2s3y restores normal spermatogonial proliferation and progression through meiotic prophase. Therefore, Eif2s3y, which encodes a subunit of the eukaryotic translation initiation factor Eif2, is Spy.

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Figure 1: Sxrb deletion interval map showing the regions covered by the Ube1y1, Dby and Eif2s3y transgenes.
Figure 2: Failure to rescue the spermatogonial proliferation defect in XSxrbO males with Ube1y1 and Dby transgenes.
Figure 3: Eif2s3y transgenes rescue the spermatogonial proliferation failure of XSxrbO males.
Figure 4: Changes in XSxrbO Eif2s3y testes with age.

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Acknowledgements

We thank R. Lovell-Badge for continuous advice and encouragement and I. Harragan for extensive histological support. S.M. thanks D. Bell and L. Teboul for instruction in transgenic techniques and J. Turner for discussions. E.M.E. thanks L. Gagnon for help with Ube1y1 transgene mapping. S.M. was the recipient of a Wellcome Travelling Fellowship; V.G., a Medical Research Fellowship; and N.S., a Studentship from MENESR. This work was supported in part by National Institutes of Health grant GM20919 (to E.M.E.) and National Cancer Institute grant CA34196 to the Jackson Laboratory.

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Authors and Affiliations

  1. Division of Developmental Genetics, MRC National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK

    Sophie Mazeyrat, Vladimir Grigoriev, Shantha K. Mahadevaiah, Obah A. Ojarikre, Áine Rattigan & Paul S. Burgoyne

  2. INSERM U491, Faculté de Medécine, 27 Boulevard Jean Moulin, Marseille, 13385 cedex 5, France

    Sophie Mazeyrat, Noëmie Saut & Michael J. Mitchell

  3. Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas, USA

    Colin Bishop

  4. The Jackson Laboratory, Bar Harbor, Maine, USA

    Eva M. Eicher

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  1. Sophie Mazeyrat
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Correspondence to Paul S. Burgoyne.

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Mazeyrat, S., Saut, N., Grigoriev, V. et al. A Y-encoded subunit of the translation initiation factor Eif2 is essential for mouse spermatogenesis. Nat Genet 29, 49–53 (2001). https://doi.org/10.1038/ng717

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