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Male-to-female sex reversal in M33 mutant mice

Nature volume 393, pages 688–692 (1998)Cite this article

Abstract

Polycomb genes in Drosophila maintain the repressed state of homeotic and other developmentally regulated genes1,2,3,4 by mediating changes in higher-order chromatin structure5,6,7. M33, a mouse homologue of Polycomb, was isolated by means of the structural similarity of its chromodomain8. The fifth exon of M33 contains a region of homology shared by Drosophila and Xenopus8,9. In Drosophila, its deletion results in the loss of Polycomb function10. Here we have disrupted M33 in mice by inserting a poly(A) capture-type neor targeting vector into its fifth exon. More than half of the resultant M33cterm/M33cterm mutant mice died before weaning, and survivors showed male-to-female sex reversal. Formation of genital ridges was retarded in both XX and XY M33cterm/M33cterm embryos. Gonadal growth defects appeared near the time of expression of the Y-chromosome-specific Sry gene11, suggesting that M33 deficiency may cause sex reversal by interfering with steps upstream of Sry. M33cterm/M33cterm mice may be a valuable model in which to test opposing views regarding sex determination.

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Figure 1: Targeted disruption of the M33 gene.
Figure 2: Male sex reversal in M33cterm/M33cterm adult mice.
Figure 3: Developmental analysis of gonads.
Figure 4: Skeletal analysis of M33cterm/M33cterm newborn.

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Acknowledgements

We thank T. Takeuchi, Y. Takihara, H. Koseki and T. Akasaka for advice and discussion; M. Djabali for communicating unpublished results; and R. A. Shiurba for critical reading of the manuscript.

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Author notes

  1. Kousei Noguchi & Toru Higashinakagawa

    Present address: Department of Biology, Waseda University, Shinjuku, Tokyo, 169-8050, Japan

Authors and Affiliations

  1. Mitsubishi Kasei Institute of Life Sciences, Machida, 194-8511, Tokyo, Japan

    Yuko Katoh-Fukui, Reiko Tsuchiya, Yoko Nakahara & Naoko Hashimoto

  2. Mammalian Genetics Laboratory, National Institute of Genetics, Mishima, 411-8540, Shizuoka, Japan

    Toshihiko Shiroishi

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  1. Yuko Katoh-Fukui
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Correspondence to Yuko Katoh-Fukui.

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Katoh-Fukui, Y., Tsuchiya, R., Shiroishi, T. et al. Male-to-female sex reversal in M33 mutant mice. Nature 393, 688–692 (1998). https://doi.org/10.1038/31482

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