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DMY is a Y-specific DM-domain gene required for male development in the medaka fish


Although the sex-determining gene Sry has been identified in mammals1, no comparable genes have been found in non-mammalian vertebrates. Here, we used recombinant breakpoint analysis to restrict the sex-determining region in medaka fish (Oryzias latipes) to a 530-kilobase (kb) stretch of the Y chromosome. Deletion analysis of the Y chromosome of a congenic XY female further shortened the region to 250 kb. Shotgun sequencing of this region predicted 27 genes. Three of these genes were expressed during sexual differentiation. However, only the DM-related2 PG17 was Y specific; we thus named it DMY. Two naturally occurring mutations establish DMY's critical role in male development. The first heritable mutant—a single insertion in exon 3 and the subsequent truncation of DMY—resulted in all XY female offspring. Similarly, the second XY mutant female showed reduced DMY expression with a high proportion of XY female offspring. During normal development, DMY is expressed only in somatic cells of XY gonads. These findings strongly suggest that the sex-specific DMY is required for testicular development and is a prime candidate for the medaka sex-determining gene.

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Figure 1: Positional cloning strategy of the sex-determining region and subsequent identification of PG17/DMY.
Figure 2: Characteristics of medaka lacking a part of the Y chromosome.
Figure 3: cDNA PCR of progeny from XYwAwr and XYwSrn female × Hd-rR male crosses.
Figure 4: PG17/DMY mRNA expression in fry gonads shown by digoxigenin-labelled in situ hybridization of larval sections.


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We are grateful to P. Koopman for advice; G. Young for critical reading of the manuscript; and M. Takeda, E. Uno and R. Hayakawa for technical assistance. This work was supported in part by Grants-in-Aid for Research for the Future from the Japan Society for the Promotion of Science, Scientific Research of Priority Area, Environmental Endocrine Disrupter Studies from the Ministry of the Environment, Bio Design from the Ministry of Agriculture, Forestry and Fisheries, and Japan Society for the Promotion of Science Research Fellowships for Young Scientists.

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Correspondence to Yoshitaka Nagahama.

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Matsuda, M., Nagahama, Y., Shinomiya, A. et al. DMY is a Y-specific DM-domain gene required for male development in the medaka fish. Nature 417, 559–563 (2002).

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