Mice Mutant in the DM Domain Gene Dmrt4 Are Viable and Fertile but Have Polyovular Follicles

Abstract

Proteins containing the DM domain, a zinc finger-like DNA binding motif, have been implicated in sexual differentiation in diverse metazoan organisms. Of seven mammalian DM domain genes, only Dmrt1 and Dmrt2 have been functionally analyzed. Here, we report expression analysis and targeted disruption of Dmrt4 (also called DmrtA1) in the mouse. Dmrt4 is widely expressed during embryonic and postnatal development. However, we find that mice homozygous for a putative null mutation in Dmrt4 develop essentially normally, undergo full sexual differentiation in both sexes, and are fertile. We observed two potential mutant phenotypes in Dmrt4 mutant mice. First, ovaries of most mutant females have polyovular follicles, suggesting a role in folliculogenesis. Second, 25% of mutant males consistently exhibited copulatory behavior toward other males. We also tested potential redundancy between Dmrt4 and two other gonadally expressed DM domain genes, Dmrt1 and Dmrt7. We observed no enhancement of gonadal phenotypes in the double mutants, suggesting that these genes function independently in gonadal development.

We thank members of the Zarkower and Bardwell laboratories and Emily Rissman, Roger Gosden, and Jurrien Dean for helpful discussions; Shinseog Kim for substantial technical advice; and Nicole Kirchhof, Ilze Matin, and Aric Frantz of the University of Minnesota Cancer Center Histopathology Core for technical assistance and expert analysis.

This work was supported by a grant from the NIH (GM59152).