Project Details
Description
DESCRIPTION: (Adapted from applicant's description): Approximately 10% of
couples world-wide are affected by reduced rates of fertility and
approximately half of these cases result from the absence of sperm production
(azoospermia) in males. Cytological analysis of patients with azoospermia
identified a deletion on the Y chromosome in a significant proportion of cases
implying a genetic component to the phenotype. This region was proposed to
contain an Azoospermia Factor (AZF). Subsequent analysis of this region
identified three distinct genes as AZF candidates one of which was termed
Deleted in Azoospermia (DAZ). Interestingly, the mouse homologue of DAZ (mDAZ)
is autosomal. Homozygous disruption of the mDAZ gene in mice results in the
absence of germ cells beyond the spermatogonial stage demonstrating the
significance of DAZ/mDAZ in spermatogenesis. The DAZ gene encodes a germ cell-
restricted cytoplasmic RNA-binding protein. Although the function of DAZ is
unknown, it appears to regulate the cytoplasmic metabolism of a target mRNA(s)
essential in spermatogenesis. Despite the identification of the DAZ gene,
progress into the function of its gene product and how it contributes to
azoospermia is limited without identification of the cognate mRNA substrate
that it binds to and regulates. We have recently devised a novel strategy to
identify natural cognate mRNA bound by RNA-binding proteins. This technique
enables rapid identification and cloning of specific cellular mRNA bound by an
RNA-binding protein. The objective of this proposal is to identify the natural
mRNA(s) which are bound by the mDAZ protein (AIM 1) and characterize the
mechanism by which mDAZ regulates these target genes and how it contributes to
spermatogenesis (AIM 2). This will provide valuable insight into the function
of DAZ in the pathogenesis of azoospermia, eventually leading to the design of
therapeutic strategies in affected individuals. Understanding how these
proteins normally function in sperm production will also provide novel
strategies in male contraception.
Status | Finished |
---|---|
Effective start/end date | 3/13/01 → 2/28/03 |
Funding
- Eunice Kennedy Shriver National Institute of Child Health and Human Development: $77,750.00
- Eunice Kennedy Shriver National Institute of Child Health and Human Development: $77,750.00
ASJC
- Genetics
- Reproductive Medicine
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