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Expression of SOX3 in the urogenital ridge is associated with XX male sex reversal in mice
Author(s) -
Thomas Paul Quinton,
Hughes James,
Tan Jacqueline,
Rogers Nicholas,
Sekido Ryohei,
LovellBadge Robin,
Sutton Edwina
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb22
Subject(s) - testis determining factor , gonadal ridge , sex reversal , biology , gonad , sexual differentiation , offspring , transgene , disorders of sex development , sox9 , embryonic stem cell , embryo , andrology , genetically modified mouse , wnt4 , genetics , medicine , gene , gene expression , endocrinology , y chromosome , pregnancy
Sox3 is expressed in the progenitor cells of the embryonic CNS and functions as a dosage‐dependent regulator of CNS development in mice and man. To further investigate the role of SOX3, we generated transgenic mice using a Sox3 genomic BAC fragment. Unexpectedly, progeny from one line (termed Sex reversed (Sr)) exhibited a markedly distorted sex ratio in favour of male offspring. Analysis of the reproductive tract in adult sex‐reversed animals indicated that all male‐specific structures were present, indicating complete XX male sex reversal. Transgene expression analysis in Sr embryos demonstrated that Sox3 is ectopically upregulated in the primordium of XX and XY gonads during sex determination due to a position effect. Importantly, morphological, gene expression and co‐transfection studies indicate that SOX3 induces testis differentiation in Sr embryonic gonads by activation of Sox9 in a mechanism analogous to that used by the Y‐linked sex determining gene Sry . Together, these data suggest that SOX3 and SRY proteins are functionally interchangeable in sex determination and provide support for the notion that Sry evolved from Sox3 via a regulatory mutation that led to its de novo expression in the early gonad.