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 of this gene is located in the testicular cord and Sertoli cells, with a small amount in the germ cells. Two copies of this 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.
^Raymond CS, Shamu CE, Shen MM, Seifert KJ, Hirsch B, Hodgkin J, Zarkower D (February 1998). "Evidence for evolutionary conservation of sex-determining genes". Nature391 (6668): 691–5. doi:10.1038/35618. PMID9490411.
^Raymond CS, Parker ED, Kettlewell JR, Brown LG, Page DC, Kusz K, Jaruzelska J, Reinberg Y, Flejter WL, Bardwell VJ, Hirsch B, Zarkower D (June 1999). "A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators". Hum. Mol. Genet.8 (6): 989–96. doi:10.1093/hmg/8.6.989. PMID10332030.
^Smith CA, Roeszler KN, Ohnesorg T, Cummins DM, Farlie PG, Doran TJ, Sinclair AH (August 2009). "The avian Z-linked gene DMRT1 is required for male sex determination in the chicken". Nature461 (7261): 267–71. doi:10.1038/nature08298. PMID19710650.
Anthony D. Krentza,b, Mark W. Murphya, Shinseog Kima,1, Matthew S. Cookc, Blanche Capelc, Rui Zhud, Angabin Matind, Aaron L. Sarvere, Keith L. Parkerf, Michael D. Griswoldg, Leendert H. J. Looijengah, Vivian J. Bardwella and David Zarkower. "The DM Domain Protein DMRT1 Is a Dose-sensitive Regulator of Fetal Germ Cell Proliferation and Pluripotency." The DM Domain Protein DMRT1 Is a Dose-sensitive Regulator of Fetal Germ Cell Proliferation and Pluripotency. PNAS, 29 Oct. 2009. Web. 12 Mar. 2014.
Christopher S. Raymond1, Emily D. Parker2, Jae R. Kettlewell1, Laura G. Brown3, David C. Page3, Kamila Kusz4, Jadwiga Jaruzelska4, Yuri Reinberg5, Wendy L. Flejter6, Vivian J. Bardwell1,2, Betsy Hirsch7 and David Zarkower1. "Human Molecular Genetics." A Region of Human Chromosome 9p Required for Testis Development Contains Two Genes Related to Known Sexual Regulators. Oxford Journal, n.d. Web. 28 Feb. 2014.
Craig A. Smith, Kelly N. Roeszler, Thomas Ohnesorg, David M. Cummins, Peter G. Farlie, Timothy J. Doran & Andrew H. Sinclair. "The Avian Z-linked Gene DMRT1 Is Required for Male Sex Determination in the Chicken." Nature.com. Nature, 26 Aug. 2009. Web. 12 Mar. 2014.
"DMRT1 Gene." - GeneCards. Crown Human Genome Center, Department of Molecular Genetics, the Weizmann Institute of Science,http://genome.ucsc.edu/. 23 Oct. 2013. Web. 12 Mar. 2014.
Ning Lei, Kaori I. Hornbaker, Daren A. Rice, Tatiana Karpova, Valentine A. Agbor, and Leslie L. Heckert. "Sex-specific Differences in Mouse DMRT1 Expression Are Both Cell Type- and Stage-dependent during Gonad Development." Sex-specific Differences in Mouse DMRT1 Expression Are Both Cell Type- and Stage-dependent during Gonad Development. NIH Public Access, 13 June 2007. Web. 12 Mar. 2014.
Smith CA, McClive PJ, Western PS; et al. (2000). "Conservation of a sex-determining gene.". Nature402 (6762): 601–2. doi:10.1038/45127. PMID10604464.
Calvari V, Bertini V, De Grandi A; et al. (2000). "A new submicroscopic deletion that refines the 9p region for sex reversal.". Genomics65 (3): 203–12. doi:10.1006/geno.2000.6160. PMID10857744.
Muroya K, Okuyama T, Goishi K; et al. (2000). "Sex-determining gene(s) on distal 9p: clinical and molecular studies in six cases.". J. Clin. Endocrinol. Metab.85 (9): 3094–100. doi:10.1210/jc.85.9.3094. PMID10999792.
Harrington JJ, Sherf B, Rundlett S; et al. (2001). "Creation of genome-wide protein expression libraries using random activation of gene expression.". Nat. Biotechnol.19 (5): 440–5. doi:10.1038/88107. PMID11329013.
Boyer A, Dornan S, Daneau I; et al. (2004). "Conservation of the function of DMRT1 regulatory sequences in mammalian sex differentiation.". Genesis34 (4): 236–43. doi:10.1002/gene.10158. PMID12434333.
Cheng HH, Ying M, Tian YH; et al. (2006). "Transcriptional diversity of DMRT1 (dsx- and mab3-related transcription factor 1) in human testis.". Cell Res.16 (4): 389–93. doi:10.1038/sj.cr.7310050. PMID16617334.
*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 w ith 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)