DMRT1 is a dose sensitivetranscription factor protein that regulates Sertoli cells and germ cells. The DMRT1 gene is located at the end of the 9th chromosome. This gene is found in a cluster with two other members of the gene family, having in common a zinc finger-like DNA-binding motif. The DM domain is an ancient, conserved component of the vertebrate sex-determining pathway that is also a key regulator of male development in flies and nematodes, and is found to be the key sex-determining factor in chickens. The majority of DMRT1 protein is located in the testicular cord and Sertolicells, with a small amount in the germ cells. This gene exhibits a gonad-specific and sexually dimorphic expression pattern, just like the related doublesex gene in fruit flies. Defective testicular development and XY feminization occur when this gene is hemizygous. Two copies of the DMRT1 gene are required for normal sexual development. When a DMRT1 gene is lost, the most common disease is chromosome 9p deletion, which causes abnormal testicular formation and feminization. The DMRT1 gene is critical for male sex determination; without this gene the default female characteristic takes over and male characteristic is slight or non-existent. When DMRT1 is knocked out in mice, the mice showed changes in both Sertoli and germ cells soon after formation of the gonadal ridge. The main defects associated with DMRT1 knockout were developmental arrest, excess proliferation of germ cells, and failure to undergo meiosis, mitosis, or migration. Thus, the knockout model shows that loss of the DMRT1 gene is associated with incomplete germ cell development leading to infertility, abnormal testicular formation, and/or feminization of the affected individual. Induced knockout of DMRT1 in adult male mice has been found to cause transdifferentiation of somatic cells in the testis to the equivalent cell types that would ordinarily be found in the ovary. Conversely, conditional expression of DMRT1 in the gonad of female mice caused the apparent transdifferentiation of ovarian somatic cells to the equivalent cell type ordinarily found in males.
