ArticleThe Journal of clinical investigation2011
Identification of SOX3 as an XX male sex reversal gene in mice and humans.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 277 citations in OpenAlex.
- Molecular Basis of Müllerian Agenesis Causing Congenital Uterine Factor Infertility-A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies.Human molecular genetics · 2018Trial
- The complete sequence of the silkworm W chromosome uncovers its rapid evolution by large-scale duplications/deletions and translocation of W-linked genes.G3 (Bethesda, Md.) · 2026Article
- Diverse SOX3 genetic variants and their associated phenotypic spectrum in human disease.Endocrine reviews · 2026Review
- Gonadal Transcriptomic Atlas Reveals Conserved and Sex-Biased Regulatory Networks in Black-Spotted Croaker (Protonibea diacanthus).Marine biotechnology (New York, N.Y.) · 2026Article
- Overexpression of SOX3 due to an X chromosome inversion leading to ovotesticular difference in sex development.Biology of sex differences · 2026Article
- The Charcot-Marie-Tooth Neuropathy (CMTX3) Complex Structural Variation Causes Differential SOX3 Spatiotemporal Expression.Human mutation · 2026Article
- Duplication of theFrontiers in genetics · 2026Article
- Neurocognitive function in males with 46,XX testicular difference of sex development.Orphanet journal of rare diseases · 2025Article
- SOX3 facilitates granulosa cell proliferation and suppresses cell apoptosis through modulating PI3K/AKT pathway by targeting SPP1.Cellular and molecular life sciences : CMLS · 2025Article
- Dose-dependent role of AMH and AMHR2 signaling in male differentiation and regulation of sex determination in Spotted knifejaw (Oplegnathus punctatus) with XCell communication and signaling : CCS · 2025Article
- How relevant is the mouse model for understanding human sex determination?International journal of biological sciences · 2025Article
- Disruption of Sex-LinkedBiomolecules · 2024Article
- Searching for the 'X' factor: investigating the genetics of primary ovarian insufficiency.Journal of ovarian research · 2024Review
- Regulation of Sex-biased Gene Expression by the Ancestral X-Y Chromosomal Gene PairbioRxiv : the preprint server for biology · 2024Article
- Whole-genome de novo sequencing reveals genomic variants associated with differences of sex development in SRY negative pigs.Biology of sex differences · 2024Article
- Comparing the roles of sex chromosome-encoded protein homologs in gene regulation.Genes & development · 2024Review
- Compensation of gene dosage on the mammalian X.Development (Cambridge, England) · 2024Review
- Prenatal detection and molecular cytogenetic characterization of Xp deletion and Xq duplication: a case report and literature review.BMC medical genomics · 2024Review
- Landscape of ConstitutionalGenes · 2024Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 9 institutions in 4 countries.
Funding
Abstract
Sex in mammals is genetically determined and is defined at the cellular level by sex chromosome complement (XY males and XX females). The Y chromosome-linked gene sex-determining region Y (SRY) is believed to be the master initiator of male sex determination in almost all eutherian and metatherian mammals, functioning to upregulate expression of its direct target gene Sry-related HMG box-containing gene 9 (SOX9). Data suggest that SRY evolved from SOX3, although there is no direct functional evidence to support this hypothesis. Indeed, loss-of-function mutations in SOX3 do not affect sex determination in mice or humans. To further investigate Sox3 function in vivo, we generated transgenic mice overexpressing Sox3. Here, we report that in one of these transgenic lines, Sox3 was ectopically expressed in the bipotential gonad and that this led to frequent complete XX male sex reversal. Further analysis indicated that Sox3 induced testis differentiation in this particular line of mice by upregulating expression of Sox9 via a similar mechanism to Sry. Importantly, we also identified genomic rearrangements within the SOX3 regulatory region in three patients with XX male sex reversal. Together, these data suggest that SOX3 and SRY are functionally interchangeable in sex determination and support the notion that SRY evolved from SOX3 via a regulatory mutation that led to its de novo expression in the early gonad.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.