Transcription factor SOX-3 is a protein that in humans is encoded by the SOX3gene.[5][6] This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic brain development and in determination of cell fate. The encoded protein acts as a transcriptional activator.[7]
Mutations in this gene have been associated with X-linked hypopituitarism (XH) and X-linked mental retardation. Patients with XH are male, have short stature, exhibit a mild form of mental retardation and present pan-hypopituitarism.[6][8] A duplication of the SOX3 gene has also been discovered to cause XX male sex reversal.[9]
SRY-box transcription factor 3, SOX3, is a transcription factor that is encoded by the SOX3 gene. This gene is responsible for ensuring proper embryonic development and determining the fate of different cells. Regarding its developmental facet, SOX3, alongside other SOX transcription factors, ensures the proper formation of the hypothalamo-pituitary axis.[10] The proper development of the hypothalamo-pituitary axis is necessary as it serves to ensure proper systemic hormonal function. When SOX3 expression is affected, the development of different structures can be affected as well. Specifically, both the hypothalamus and the pituitary gland can suffer in accomplishing proper growth. Due to this, conditions such as hypopituitarism and mental retardation are found in cases with a lack of SOX3. Also, craniofacial abnormalities can be seen as a result of a lack of the SOX3 gene. To aid in the further understanding of the SOX3 gene, mice have been used as knockout models to study the effects of the gene’s absence.[11]
Function
SOX3 belongs to the family of SRY-related HMG-box containing genes which behave as transcription factors. SOX3 has been found to be involved in the regulation of embryonic brain development, the determination of cell fate and in XX male sex reversal.[7]
SOX3 contains a single exon and is found in a highly conserved region of the X chromosome. The SOX3 gene shares some conservation with the SRY gene, and encodes a protein that is similar, sharing 67% amino acid identity across the DNA-binding HMG domain.[12] This has led to the hypothesis that the SRY gene arose from SOX3 through a gain of function mutation within the proto-Y chromosome. Evidence to support this hypothesis arose from the discovery of a rare human case of XX sex reversal, that is thought to have occurred through a de novo duplication of the SOX3 gene.[9] Such a duplication is thought to result in a gain of function expression of SOX3 in the genital ridge of the developing embryo leading to XX male sex reversal.
^ abMoalem S, Babul-Hirji R, Stavropolous DJ, Wherrett D, Bägli DJ, Thomas P, et al. (July 2012). "XX male sex reversal with genital abnormalities associated with a de novo SOX3 gene duplication". American Journal of Medical Genetics. Part A. 158A (7): 1759–1764. doi:10.1002/ajmg.a.35390. PMID22678921. S2CID6220503.
^“SOX3 SRY-Box Transcription Factor 3 [Homo Sapiens (Human)] - Gene - NCBI.” National Center for Biotechnology Information, U.S. National Library of Medicine, www.ncbi.nlm.nih.gov/gene/6658.
Kamachi Y, Uchikawa M, Kondoh H (April 2000). "Pairing SOX off: with partners in the regulation of embryonic development". Trends in Genetics. 16 (4): 182–187. doi:10.1016/S0168-9525(99)01955-1. PMID10729834.
Stevanović M, Lovell-Badge R, Collignon J, Goodfellow PN (December 1993). "SOX3 is an X-linked gene related to SRY". Human Molecular Genetics. 2 (12): 2013–2018. doi:10.1093/hmg/2.12.2013. PMID8111369.
Collignon J, Sockanathan S, Hacker A, Cohen-Tannoudji M, Norris D, Rastan S, et al. (February 1996). "A comparison of the properties of Sox-3 with Sry and two related genes, Sox-1 and Sox-2". Development. 122 (2): 509–520. doi:10.1242/dev.122.2.509. PMID8625802.
Aota S, Nakajima N, Sakamoto R, Watanabe S, Ibaraki N, Okazaki K (May 2003). "Pax6 autoregulation mediated by direct interaction of Pax6 protein with the head surface ectoderm-specific enhancer of the mouse Pax6 gene". Developmental Biology. 257 (1): 1–13. doi:10.1016/S0012-1606(03)00058-7. PMID12710953.
Dattani MT (December 2003). "Borjeson-Forssman-Lehmann syndrome: a novel pituitary phenotype due to mutation in a novel gene". Journal of Pediatric Endocrinology & Metabolism. 16 (9): 1207–1209. doi:10.1515/jpem.2003.16.9.1207. PMID14714741. S2CID45542882.
Raverot G, Lejeune H, Kotlar T, Pugeat M, Jameson JL (August 2004). "X-linked sex-determining region Y box 3 (SOX3) gene mutations are uncommon in men with idiopathic oligoazoospermic infertility". The Journal of Clinical Endocrinology and Metabolism. 89 (8): 4146–4148. doi:10.1210/jc.2004-0191. PMID15292361. S2CID24592833.
