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SOX9

17q24.1-25.1 Entrez:549607 ENSG00000125398 NCBI:6662

Friday 4 July 2003

Definition: The human SOX9 gene, located in chromosome region 17q24.1-25.1, encodes a transcription factor involved in chondrogenesis, testis and pancreas development.

The SRY-related SOX9 gene is involved in both chondrogenesis and the early steps of mammalian sex determination.

SOX9 cooperative dimerization is required for chondrogenesis but not for sex determination and may explain why campomelic dysplasia need not be associated with XY sex reversal (12837698).

Images

Images

- PAX2, SOX9 cartography of the Developing Urogenital System

- SOX9 - 3D cartography of the developing pancreas

Pathology

- haploinsufficiency of SOX9 by germline mutations or 17q deletions (10213041) in

  • campomelic dysplasia (MIM.114290)
  • +/- male-to-female sex reversal in most, but not all, XY individuals

- duplication of SOX9 in autosomal XX sex reversal (10588843)

    • penile hypospadias
    • scrotal hypospadias

- SOX9-associated disorder of sexual differentiation

Diagnostic pathology

- SOX-9 is apparently common to both notochordal and cartilaginous differentiation, and is not useful in the chordoma-chondrosarcoma differential diagnosis. (18820665)

Immunochemistry

- cells in seminiferus ducts of the testis
- Distinct nuclear staining in most tissues, both normal and malignant. - Gastrointestinal canal, showed positivity mainly towards base of crypts. - Additional cytoplasmic positivity seen in few cases for exemple in pancreas acini, ducts were nuclear positive.
- Almost the same pattern was seen in salivary glands.
- Lymphatic tissue was almost negative, but in follicle center few cells showed nuclear positivity.
- Tumors showed often a strong nuclear expression.
- All lymphomas were negative.

Animal models

- Sox9-haploinsufficiency causes glucose intolerance in mice. (21829703)

Reviews

- Koopman P. Sex determination: a tale of two Sox genes. Trends Genet. 2005 Jul;21(7):367-70. PMID: 15949865

- Harley VR, Clarkson MJ, Argentaro A. The molecular action and regulation of the testis-determining factors, SRY (sex-determining region on the Y chromosome) and SOX9. Endocr Rev. 2003 Aug;24(4):466-87. PMID: 12920151

- Clarkson MJ, Harley VR. Sex with two SOX on: SRY and SOX9 in testis development. Trends Endocrinol Metab. 2002 Apr;13(3):106-11. PMID: 11893523

References

- Sox9-haploinsufficiency causes glucose intolerance in mice. Dubois CL, Shih HP, Seymour PA, Patel NA, Behrmann JM, Ngo V, Sander M. PLoS One. 2011;6(8):e23131. PMID: 21829703 (Free)

- FOXL2 and SOX9 as parameters of female and male gonadal differentiation in patients with various forms of disorders of sex development (DSD). Hersmus R, Kalfa N, de Leeuw B, Stoop H, Oosterhuis JW, de Krijger R, Wolffenbuttel KP, Drop SL, Veitia RA, Fellous M, Jaubert F, Looijenga LH. J Pathol. 2008 May;215(1):31-8. PMID: 18348162

- Oakley GJ, Fuhrer K, Seethala RR. Brachyury, SOX-9, and podoplanin, new markers in the skull base chordoma vs chondrosarcoma differential: a tissue microarray-based comparative analysis. Mod Pathol. 2008 Sep 26. PMID: 18820665