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The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis

Nature volume 389, pages 73–77 (1997)Cite this article

RBM and DAZ/SPGY are two families of genes located on the Y chromosome that encode proteins containing RNA-binding motifs, and both have been described as candidate human spermatogenesis genes1,2. Transmission of deletions from father to son has been observed in the case of DAZ3,4,5, but neither gene family has been shown to be essential for spermatogenesis in human males. The DAZ/SPGY genes are particularly amenable to a knockout approach, as they are found on the Y chromosome in Old World primates and apes6, but in other mammals, they are represented only by an autosomal gene, DAZLA7,8,9,10, which is also present in Old World primates and apes. It has also been shown that a Dazla homologue is essential for spermatogenesis in Drosophila11. Here we show that Dazla protein is cytoplasmic in male and female germ cells, unlike the nuclear RBM protein12. Disruption of the Dazla gene leads to loss of germ cells and complete absence of gamete production, demonstrating that Dazla is essential for the differentiation of germ cells.

These observations suggest that germ cells are reduced in the gonads, as a result of either reduced proliferation in the fetus or loss of germ cells after proliferation. To distinguish between these possibilities we analysed one litter at 15 days post-coitum (d.p.c.) and one at 19 d.p.c. The DazlaTm1Hgu/DazlaTm1Hguovaries at 15 d.p.c. appear relatively normal, with many early pachytene cells (Fig. 3d–f), but by 19 d.p.c. there is a marked deficiency of oocytes, with many of those remaining undergoing atresia (Fig. 3g, h). Testes of 15 d.p.c. DazlaTm1Hgu/DazlaTm1Hgumice are similar to those of DazlaTm1Hgu/+ animals (Fig. 4a, b), but by 19 d.p.c. they have sparse tubule populations (Fig. 4c–e). Sertoli-cell : germ-cell ratios are increased from 4 : 1 in wild-type to 8 : 1 in both DazlaTm1Hgu/+ and DazlaTm1Hgu/DazlaTm1Hguanimals. Meiosis has not initiated by this stage, and so this loss of germ cells cannot be dependent on pachytene arrest.

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Figure 1: Distribution of Dazla protein in gonads.
Figure 2: Targeting of Dazla.
Figure 3: Histological analyses of ovaries.
Figure 4: Testis histology.
Figure 5: Abnormal sperm production in heterozygotes.

References

  1. Reijo, R.et al. Diverse spermatogenic defects in humans caused by Y-chromosome deletions encompassing a novel RNA-binding protein gene. Nature Genet. 10, 383–393 (1995).

    Google Scholar 

  2. Ma, K.et al. AY-chromosome gene family with RNA-binding protein homology candidates for the azoospermia factor AZF controlling human spermatogenesis. Cell 75, 1287–1295 (1993).

    Google Scholar 

  3. Reijo, R., Alagappan, R. K., Patrizio, P. & Page, D. C. Severe oligozoospermia resulting from deletions of azoospermia factor gene on Y-chromosome. Lancet 347, 1290–1293 (1996).

    Google Scholar 

  4. Vogt, P. H.et al. Human Y-chromosome azoospermia factors (azf) mapped to different subregions in Yq11. Hum. Mol. Genet. 5, 933–943 (1996).

    Google Scholar 

  5. Nakahori, Y.et al. The Y-chromosome region is essential for spermatogenesis. Horm. Res. 46, 20–23 (1996).

    Google Scholar 

  6. Shan, Z. H.et al. ASPGY copy homologous to the mouse gene Dazla and the Drosophila gene boule is autosomal and expressed only in the human male gonad. Hum. Mol. Genet. 5, 2005–2011 (1996).

    Google Scholar 

  7. 7. Cooke, H. J., Lee, M., Kerr, S. & Ruggiu, M. A. Amurine homolog of the human DAZ gene is autosomal and expressed only in male and female gonads. Hum. Mol. Genet. 5, 513–516 (1996).

    Google Scholar 

  8. Reijo, R.et al. Mouse autosomal homolog of DAZ, a candidate male-sterility gene in humans, and is expressed in male germ-cells before and after puberty. Genomics 35, 346–352 (1996).

    Google Scholar 

  9. Saxena, R.et al. The DAZ gene cluster on the human Y chromosome arose from an autosomal gene that was transposed, repeatedly amplified and pruned. Nature Genet. 14, 292–298 (1996).

    Google Scholar 

  10. Yen, P. H., Chai, N. N. & Salido, E. C. The human autosomal gene dazla – testis specificity and a candidate for male-infertility. Hum. Mol. Genet. 5, 2013–2017 (1996).

    Google Scholar 

  11. Eberhart, C. G., Maines, J. Z. & Wasserman, S. A. Meiotic cell cycle requirement for a fly homologue of human Deleted in Azoospermia. Nature 381, 783–785 (1996).

    Article  ADS  CAS  Google Scholar 

  12. Elliott, D. J.et al. Expression of RBM in the nuclei of human germ cells is dependent on a critical region of the Y chromosome long arm. Proc. Natl Acad. Sci. USA 94, 3848–3853 (1997).

    Google Scholar 

  13. Niederberger, C., Agulnik, A. I., Cho, Y., Lamb, D. & Bishop, C. E. In situ hybridization shows that Dazla expression in mouse testis is restricted to premeiotic stages iv–vi of spermatogenesis. Mamm. Genome 8, 227–278 (1997).

    Google Scholar 

  14. Bleil, J. D. & Wassarman, P. M. Synthesis of zona pellucida proteins by denuded and follicle-enclosed mouse oocytes during culture in vitro. Proc. Natl Acad. Sci. USA 77, 1029–1033 (1980).

    Google Scholar 

  15. Bleil, J. D. & Wassarman, P. M. Structure and function of the zona pellucida: identification and characterization of the proteins of the mouse oocyte's zona pellucida. Dev. Biol. 76, 185–202 (1980).

    Google Scholar 

  16. Pelliniemi, L. J., Frojdman, K. & Paranko, J. in The Serotoli Cell(eds Russell, L. D. &Griswold, M. D.) 87–114 (Cashe River, Clearwater, FL, (1993)).

    Google Scholar 

  17. Searle, A. G. & Beechey, C. V. Sperm-count, egg-fertilisation and dominant lethality after X-irradiation of mice. Mut. Res. 22, 63–77 (1974).

    Google Scholar 

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Acknowledgements

We thank all our colleagues in the Human Genetics Unit who helped in the discussion and production of this paper. This work was supported by the MRC. M.R. is supported by an Italian Telethon grant.

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Author notes

  1. Howard J. Cooke: Correspondence and requests for materials should be addressed to H.J.C.

Authors and Affiliations

  1. MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK

    Matteo Ruggiu, Robert Speed, Mary Taggart, Stewart J. McKay, Fiona Kilanowski, Philippa Saunders & Julia Dorin

  2. MRC Reproductive Biology Unit, 37 Chalmers Street, Edinburgh, EH3 9EW, UK

    Philippa Saunders

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  1. Matteo Ruggiu
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Ruggiu, M., Speed, R., Taggart, M. et al. The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis. Nature 389, 73–77 (1997). https://doi.org/10.1038/37987

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