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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.

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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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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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