DMRT1
Protein-coding gene in humans
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Doublesex and mab-3 related transcription factor 1, also known as DMRT1, is a protein which in humans is encoded by the DMRT1 gene.[5][6][7]
Gene
In humans, the DMRT1 gene is located at the end of chromosome 9. This gene is found in a cluster with two other members of the gene family.
In birds, DMRT1 is located on the Z chromosome and male sexual development is determined by dosage of this gene.[8]
Structure
DMRT1 belongs to a gene family characterized by a zinc finger-like DNA-binding motif known as the DM domain. 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 birds.[9]
The majority of DMRT1 protein is located in the testicular cord and Sertoli cells, with a small amount present in germ cells.
Function
DMRT1 is a dose-sensitive transcription factor that regulates Sertoli cells and germ cells.
Two copies of the DMRT1 gene are required for normal sexual development. The gene is critical for male sex determination; in its absence, female developmental pathways predominate and male characteristics are reduced or absent.
When DMRT1 is knocked out in mice, changes occur in both Sertoli and germ cells soon after formation of the gonadal ridge. The principal defects associated with DMRT1 knockout include developmental arrest, excess proliferation of germ cells, and failure to undergo meiosis, mitosis, or migration. Thus, the knockout model shows that loss of DMRT1 is associated with incomplete germ cell development leading to infertility, abnormal testicular formation, and/or feminization of the affected individual.[citation needed]
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 ordinarily found in the ovary.[10]
Conversely, conditional expression of DMRT1 in the gonad of female mice caused apparent transdifferentiation of ovarian somatic (granulosa) cells to the equivalent male cell type (Sertoli).[11]
Clinical significance
Defective testicular development and XY feminization occur when this gene is hemizygous.[5]
Loss of one copy of DMRT1 most commonly occurs in chromosome 9p deletion, which causes abnormal testicular formation and feminization.