18th International Mouse Genome Conference
17-22 October 2004, Seattle, USA
Plenary Presentations * Oral
Presentations * Poster
Abstracts * Photos
Verne Chapman Memorial Lecture * Table
of Contents * Attendees * Awards
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.