International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 22 - FERTILE XY(SRY-) MALES

Qin Y 1, Bishop CE 2

1 Baylor College of Medicine, department of OB/GYN, Houston, United States, 2 Baylor College of Medicine, dept. Molecular & Human Genetics, Houston, United States

We have previously reported the dominant mouse mutant Odd Sex (Ods) in which XX Ods/+ mice, develop as phenotypic males due to male-pattern expression of Sox9 in developing XX Ods/+ embryonic gonads. The testis of XX Ods/+ males are small, devoid of germ cells, and the adults are sterile. This is to be expected as such males  lack all Y chromosome encoded fertility genes and the presence of two copies of the X chromosome in the germ line has been shown to be incompatible with the early post natal mitotic divisions of spermatogenesis. In order to test whether, the specific activation of  Sox9, in embryonic XX Ods/+ gonads was sufficient to initiate the development of a fully functional adult testis and a fertile male, we constructed an XY (Sry-), Ods/+ male which carries one copy of the X, and all Y genes except Sry. Such males were normaly fertile up to 4-5 months of age indicating that Sox9 then. Unexpectedly XY Ods/+ males became sterile by 6-8 months in contrast to XY TgSry+ or XY TgSry+, Ods/+ littermates who remained fully fertile.  When compared to normal XY FVB males, we noticed that the vasculature pattern in adult XY Ods/+ testis was disrupted, whereas that of XY TgSry+ and XY TgSry+, Ods/+ showed the normal pattern. These finding correlate with the failure of XX Ods/+ males to downregulate Wnt4 at E11.5. To test whether this was due to Sry itelf or the level of Sox9, we constructed an XY Ods/Ods homozygote male. In this mouse the testicular vascular pattern was restored to normal. These data indicate that activation of the male sex-determining pathway by Sox9 is sufficient to produce a fully functional testis and a fertile male. They indicate that all genes in this pathway, upstream of Sox9, muts be regulatory in nature. They indicate that subtle changes in gene dosage of Sox9 and Wnt4 can result in anomalies of vascularisation that have a progressive impact on male fertility over time.

[an error occurred while processing this directive]