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Sry requires a CAG repeat domain for male sex determination in Mus musculus

Nature Genetics volume 22, pages 405–408 (1999)Cite this article

Abstract

SRY, the mammalian Y-chromosomal sex-determining gene1,2,3, encodes a protein characterized by a DNA-binding and -bending domain referred to as the HMG box4,5. Despite the pivotal role of this gene, only the HMG box region has been conserved through evolution6,7, suggesting that SRY function depends solely on the HMG box and therefore acts as an architectural transcription factor8. In mice (genus Mus) Sry also includes a large CAG trinucleotide repeat region encoding a carboxy-terminal glutamine-rich domain that acts as a transcriptional trans-activator in vitro9. The absence of this or any other potential trans-activating domain in other mammals1,9, however, has raised doubts as to its biological relevance. To test directly whether the glutamine-rich region is required for Sry function in vivo, we created truncation mutations of the Mus musculus musculus Sry gene and tested their ability to induce testis formation in XX embryos using a transgenic mouse assay. Sry constructs that encode proteins lacking the glutamine-rich region were unable to effect male sex determination, in contrast to their wild-type counterparts. We conclude that the glutamine-rich repeat domain of the mouse Sry protein has an essential role in sex determination in vivo, and that Sry may act via a fundamentally different biochemical mechanism in mice compared with other mammals.

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Figure 1: The mouse Sry protein.
Figure 2: Constructs used in this study and ability of each to cause sex reversal.
Figure 3: SryStop2 transgene expression in 11.
Figure 4: Size and DNA binding properties of mutant Sry proteins.

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Acknowledgements

We thank R. Lovell-Badge for providing plasmid L741 and for helpful discussions; C. Nagamine for comments on the manuscript; anonymous referees for constructive suggestions; R. Behringer, R. Krumlauf, A. Greenfield, S. Wheatley, Y. Kanai, M. Azuma-Kanai, D. Pennisi and M. Hargrave for advice and encouragement; and L. Kelly and A. Hardacre for supply of mice. This work was supported by an NHMRC Postdoctoral Research Fellowship to J. Bowles and research grants from the NHMRC and the Australian Research Council.

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  1. Centre for Molecular and Cellular Biology, The University of Queensland, Brisbane, 4072, Queensland, Australia

    Josephine Bowles, Leanne Cooper, Jennifer Berkman & Peter Koopman

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  1. Josephine Bowles
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Correspondence to Peter Koopman.

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Bowles, J., Cooper, L., Berkman, J. et al. Sry requires a CAG repeat domain for male sex determination in Mus musculus. Nat Genet 22, 405–408 (1999). https://doi.org/10.1038/11981

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