Female-to-male sex reversal in mice caused by transgenic overexpression of Dmrt1

• DOI: 10.1242/dev.122184
• Publication Date: 2015-02-28T03:44:46Z
• Authors: Liang Zhao; Terje Svingen; Ee Ting Ng; Peter Koopman
• Keywords: Testis determining factor; WNT4; SOX9; FGF9; Sexual Differentiation; Sex reversal

Genes related to Dmrt1, which encodes a DNA-binding DM domain transcription factor, act as triggers for primary sex determination in broad range of metazoan species. However, this role is fulfilled mammals by Sry, newly evolved gene on the Y chromosome, such that Dmrt1 has become dispensable and instead maintains Sertoli cell phenotype postnatal testes. Here, we report enforced expression XX mouse fetal gonads using Wt1-BAC transgene system sufficient drive testicular differentiation male secondary development. transgenic showed typical size vasculature. Key ovarian markers, including Wnt4 Foxl2, were repressed. cells expressing hallmark testis-determining Sox9 formed, although they did not assemble into normal testis cords. Other bipotential lineages differentiated types, steroidogenic Leydig non-meiotic germ cells. As consequence, internal external reproductive organs developed postnatally, with an absence female tissues. These results reveal retained its ability trigger mammals, even though function no longer normally required. Thus, provides common thread evolution mechanisms metazoans.