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 (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 chickens. 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.
The DMRT1 gene is located at the end of the 9th chromosome. This gene is a dose sensitive transcription factor protein that regulates Sertoli cells and germ cell. The majority DMRT1 protein is located in the testicular cord and Sertoli cells, with a small amount in the germ cells. 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 in the male sex determination and without this gene the default female characteristic takes over and male characteristic is slight or non-existent. In the knockout model of this gene, the mice showed changes in both Sertoli and germ cells soon after the gonadal ridge was formed. The main defects associated with this knockout gene 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.
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*1. A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators. (PubMed id 10332030)1, 2, 3, 9 Raymond C.S.... Zarkower D. (1999)
2. Evidence for evolutionary conservation of sex-determining genes. (PubMed id 9490411)1, 2, 3, 9 Raymond C.S....Zarkower D. (1998)
3. Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer. (PubMed id 20543847)1, 2, 4 Turnbull C....Rahman N. (2010)
4. Transcriptional diversity of DMRT1 (dsx- and mab3-related transcription factor 1) in human testis. (PubMed id 16617334)1, 2, 9 Cheng H.H....Zhou R.J. (2006)
5. A new submicroscopic deletion that refines the 9p region for sex reversal. (PubMed id 10857744)1, 2, 9 Calvari V.... Guioli S. (2000)
6. A second independent locus within DMRT1 is associated with testicular germ cell tumor susceptibility. (PubMed id 21551455)1, 4 Kanetsky P.A....Nathanson K.L. (2011)
7. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)1, 4 Rose J.E....Uhl G.R. (2010)
8. DNA sequence and analysis of human chromosome 9. (PubMed id 15164053)1, 2 Humphray S.J.... Dunham I. (2004)
9. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1,2 Gerhard D.S....Malek J. (2004)
10. The DM domain protein DMRT1 is a dose-sensitive regul ator of fetal germ cell proliferation and pluripotency. (PubMed id 20007774)1, 9 Krentz A.D....Zarkower D. (2009)