Would testes be produced? If SRY is functional, can it produce other proteins that can direct the production of testes, which may or may not be sterile?


Quoting the abstract of this paper verbatim:

Sox9 is an Sry-box-containing gene that encodes a transcriptional activator. During mouse gonadogenesis, Sox9 is detected in the male gonad at 11.5 days postcoitus (dpc). At 12.5 dpc, testicular cords form, morphologically distinguishing the male gonad from the ovary. From this stage onwards, Sox9 expression is restricted to the Sertoli cell lineage and persists in the adult. Humans with heterozygous mutations in SOX9 develop a skeletal syndrome known as campomelic dysplasia. Furthermore, most XY SOX9 heterozygotes show variable male-to-female sex reversal, implicating SOX9 in testis development. Sox9 heterozygous knockout mice die at birth with a syndrome similar to that of human campomelic dysplasia. In contrast to humans, XY Sox9+/- mice form normal appearing testes. Germ-line knockout of Sox9 using a conditional null allele provides a tool for generating Sox9-/- mice by simple genetic crosses. However, Sox9-/- mice die soon after 11.5 dpc because of cardiovascular defects. In vitro culture of the urogenital ridges of XY Sox9-/- results in gonads lacking testicular cords and Sertoli cell marker expression, but with the expression of ovarian-specific markers. Therefore, Sox9 is essential for diverting an intrinsically ovarian program of organogenesis toward testis formation.

From MGI page on Sox9:

Null mutant heterozygotes and conditional knockout mutants display perinatal lethality with cleft palate, hypoplasia and distortion of numerous cartilage-derived skeletal structures, and premature mineralization in many bones. Specific conditional knockout mutations are sex-reversed.


SOX9 is indeed the factor which is important for the developent of the sexual organs and not only for men, but also for women. Expression of SOX9 regulates the expression of the anti-Müllerian Hormone, which inhibits the formation of the female reproduction system. See reference 1 for more details.

Mutations in or around (in regulatory regions) of the SOX9 gene lead to severe developmental changes and to the genetic disorder "Campomelic dysplasia". The disorder leads to changes in the bones and also in the sex determination, it is often lethal in the neonatal period due to respiratory problems. Have a look into reference 2 for more details.

In mice, the complete loss of SOX9 is embryonical lethal, have a look at reference 3 for details. Although there are no data available for humans (for obvious ethical reasons) I assume that the effect is the same.

Development of testis starts by the activation of SOX9 by the testis determination factor. SOX9 in turn activates a number of other transcription factors (have a look into references 4 and 5 for details) which finally lead to the development of the testis.

Mutations in SOX9 in men (with XY chromosomes) also lead to the reversal of the sex, meaning these individuals will develop female reproduction organs (see reference 4). It has also been shown that female mice will develop testis when SOX9 is induced in these animals (see reference 6). You can also have a look into the OMIM database for an extensive review.


  1. Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Müllerian hormone gene.
  2. A clinical and genetic study of campomelic dysplasia.
  3. Sex determination: a tale of two Sox genes
  4. The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation.
  5. Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination.
  6. Sox9 induces testis development in XX transgenic mice

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