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Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132
Address all correspondence and requests for reprints to: Dr. Eli Y. Adashi, Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, 546 Chipeta Way, ARUP II, Box 20, Salt Lake City, Utah 84108. E-mail: eadashi{at}hsc.utah.edu
The importance of several ovary-selective/specific genes,
i.e. genes preferentially or exclusively expressed in
the ovary, has been established. Indeed, null mutant female mice for
the c-mos, growth and differentiation factor-9,
-inhibin, and zona pellucida-3 genes proved sterile. A loss of
function mutation of the human FSH receptor gene established its
critical role in ovarian function. These data support the hypothesis
that genes expressed selectively or specifically in the ovary are
probably essential for the normal functioning of this organ system. We
have used the differential screening technique suppression subtractive
hybridization to systematically isolate and clone genes that are
expressed in an ovary-selective/specific manner. The resultant target
complementary DNA (cDNA) library has been exhaustively screened to a
point at which additional sequencing was increasingly unlikely (
4%)
to yield additional previously unencountered cDNAs. In
toto, 844 clones were sequenced and analyzed for homology to
known genes using the Basic Local Alignment Tool (BLAST). Of those, 342
were determined to be independent (nonredundant). One hundred and
fifty-nine independent clones proved identical to previously
characterized genes, whereas an additional 100 independent clones
proved significantly homologous (but not identical) to previously
characterized genes. Yet 83 other independent clones did not display
significant homology to previously characterized genes now listed in
the publicly accessible nonredundant databases. As such, these latter
genes were deemed novel. Of these 83 novel genes, a total of 36
displayed ovary-specific/selective expression, as determined by probing
mouse multitissue Northern blots with
32P-labeled/PCR-amplified cDNA inserts. Under these
circumstances, the false positive rate was minimal, as only one novel
clone was expressed at a higher level in nonovarian tissues relative to
ovary. Of the 36 ovary-specific/selective novel genes, 22 proved
subject to hormonal regulation during a simulated estrous cycle. In
this communication we focus on 2 such novel
ovary-specific/hormonally-dependent genes, the full-length sequences of
which were isolated using rapid amplification of 3'-cDNA ends
technology. Taken together, the present study accomplished systematic
identification of those genes that are restricted in their expression
to the ovary. These ovary-selective genes may have significant
implications for the understanding of ovarian function in molecular
terms and for the development of innovative strategies for the
promotion of fertility or its control.
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