TY - JOUR
T1 - A transgenic insertion upstream of Sox9 is associated with dominant XX sex reversal in the mouse
AU - Bishop, Colin E.
AU - Whitworth, Deanne J.
AU - Qin, Yanjun
AU - Agoulnik, Alexander I.
AU - Agoulnik, Irina U.
AU - Harrison, Wilbur R.
AU - Behringer, Richard R.
AU - Overbeek, Paul A.
N1 - Funding Information:
We thank G. Schuster for microinjections; L. Vien for animal husbandry and PCR assays; B. de Crombrugghe for the Sox9 in situ hybridization probe; H. Boettger-Tong for advice on several aspects of the work; and B. Capel and P. Koopman for discussion on the manuscript. Supported by grants from the National Institutes of Health (to C.E.B., R.R.B. and P.A.O.).
PY - 2000
Y1 - 2000
N2 - In most mammals, male development is triggered by the transient expression of the Y-chromosome gene, Sry, which initiates a cascade of gene interactions ultimately leading to the formation of a testis from the indifferent fetal gonad. Several genes, in particular Sox9, have a crucial role in this pathway. Despite this, the direct downstream targets of Sry and the nature of the pathway itself remain to be clearly established. We report here a new dominant insertional mutation, Odsex (Ods), in which XX mice carrying a 150-kb deletion (approximately 1 Mb upstream of Sox9) develop as sterile XX males lacking Sry. During embryogenesis, wild-type XX fetal gonads downregulate Sox9 expression, whereas XY and XX Ods/+ fetal gonads upregulate and maintain its expression. We propose that Ods has removed a long-range, gonad-specific regulatory element that mediates the repression of Sox9 expression in XX fetal gonads. This repression would normally be antagonized by Sry protein in XY embryos. Our data are consistent with Sox9 being a direct downstream target of Sry and provide genetic evidence to support a general repressor model of sex determination in mammals.
AB - In most mammals, male development is triggered by the transient expression of the Y-chromosome gene, Sry, which initiates a cascade of gene interactions ultimately leading to the formation of a testis from the indifferent fetal gonad. Several genes, in particular Sox9, have a crucial role in this pathway. Despite this, the direct downstream targets of Sry and the nature of the pathway itself remain to be clearly established. We report here a new dominant insertional mutation, Odsex (Ods), in which XX mice carrying a 150-kb deletion (approximately 1 Mb upstream of Sox9) develop as sterile XX males lacking Sry. During embryogenesis, wild-type XX fetal gonads downregulate Sox9 expression, whereas XY and XX Ods/+ fetal gonads upregulate and maintain its expression. We propose that Ods has removed a long-range, gonad-specific regulatory element that mediates the repression of Sox9 expression in XX fetal gonads. This repression would normally be antagonized by Sry protein in XY embryos. Our data are consistent with Sox9 being a direct downstream target of Sry and provide genetic evidence to support a general repressor model of sex determination in mammals.
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U2 - 10.1038/82652
DO - 10.1038/82652
M3 - Article
C2 - 11101852
AN - SCOPUS:0033662409
SN - 1061-4036
VL - 26
SP - 490
EP - 494
JO - Nature Genetics
JF - Nature Genetics
IS - 4
ER -