Open Close
General Information
Name
azoospermia, Sertoli-cell-only syndrome, DDX3-related
FlyBase ID
FBhh0000542
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes a fly model of azoospermia, Sertoli cell-only syndrome. In humans, there are both Y-linked and X-linked forms of this syndrome. Hypomorphic mutations in the Drosophila gene bel, which encodes a DEAD-box RNA helicase, have been found to result in the specific loss of germline cells in the testis, whereas somatic cells are maintained; this phenotype recapitulates that observed for Sertoli cell-only syndrome. Classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for the Dmel\bel gene.

One of the two human orthologs of Dmel\bel, DEAD-box helicase 3, Y-linked (DDX3Y), is within the region of the Y chromosome implicated in Sertoli cell-only syndrome. The second orthologous human gene, DDX3X, is located on the X chromosome. Neither human gene has been introduced into flies.

Homozygous amorphic alleles of Dmel\bel are lethal; hypomorphic mutations result sterility or semi-sterility in both sexes. Unlike the human DDX3 genes, the Dmel\bel gene is located on an autosomal chromosome; there are no closely related paralogs in Drosophila. Genetic and physical interactions of Dmel\bel have been described; see below and in the bel gene report.

[updated Jun. 2017 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: azoospermia, non-obstructive
Symptoms and phenotype
Non-obstructive azoospermia (NOA) is defined as absence of any measurable level of sperm in semen, resulting from a defect in the production of spermatozoa in the testes. [from MedGen, Non-obstructive azoospermia; MedGen UID: 866757]
Non-obstructive azoospermia (NOA), or failure of spermatogenesis within the testis, is diagnosed in approximately 10% of infertile men. NOA may be due to a lack of appropriate stimulation by gonadotropins, in which case hormonal therapy is usually effective. A larger category of non-obstructive azoospermia consists of men with an intrinsic testicular impairment. In these cases, the primary approach is to improve the quantity and quality of sperm retrieved from the testis for use for in vitro fertilization (Kumar, 2013; PMCID:PMC3583162).
Specific Disease Summary: azoospermia, Sertoli-cell-only syndrome, DDX3-related
OMIM report
[SPERMATOGENIC FAILURE, Y-LINKED, 1; SPGFY1](https://omim.org/entry/400042)
Human gene(s) implicated
[SPERMATOGENIC FAILURE, Y-LINKED, 1; SPGFY1](https://omim.org/entry/400042)
Symptoms and phenotype
In the evaluation of male infertility, the Sertoli cell-only (SCO) syndrome is diagnosed on testicular biopsy when either no germ cells are visible in any seminiferous tubules (SCO type I) or germ cells are present in a minority of tubules (SCO type II) (Sargent et al., 1999; pubmed:10507722). [from OMIM:305700, OMIM:400042; 2017.06.01]
Sertoli cells are somatic cells of the testis; they are found in the seminiferous tubules, where meiosis occurs and the spermatozoa are produced.
Genetics
There are Y-linked (OMIM:400042)and X-linked (OMIM:305700) forms of Sertoli cell-only syndrome. The Y-linked form has been associated with deletions of the 'azoospermia factor' (AZF) region; this region includes several genes, one of which is DDX3Y (DEAD-box helicase 3, Y-linked). [from OMIM:400042; 2017.06.01] There is also a DEAD-box helicase 3 gene on the X-chromosome (DDX3X). [from OMIM:300160; 2017.06.01]
Cellular phenotype and pathology
Molecular information
External links
Disease synonyms
SCO
spermatogenic failure, X-linked, 1
spermatogenic failure, Y-linked, 1
Sertoli cell-only syndrome
germinal cell aplasia
del Castillo syndrome
azoospermia, Sertoli cell-only syndrome, DDX3-related
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)
    Many to one: 2 human to 1 Drosophila; the 2 human genes are DDX3Y and DDX3X.
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)
    Many to one: 2 human to 1 Drosophila; the 2 human genes are DDX3Y and DDX3X.
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      belle (bel) encodes a DEAD-box RNA helicase that functions both as positive and negative translation regulator. It is essential for embryo viability and fertility, and is required for the maintenance of male germ-line stem cells. [Date last reviewed: 2019-05-16]
      Gene Groups / Pathways
        Comments on ortholog(s)
        High-scoring ortholog of human DDX3Y and DDX3X (1 Drosophila to 2 human); Dmel\bel shares 51% identity and 61% similarity with the human genes.
        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        Synthetic Gene(s) Used (0)
        Summary of Physical Interactions (20 groups)
        RNA-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, primer specific pcr
        anti tag coimmunoprecipitation, quantitative reverse transcription pcr
        anti tag coimmunoprecipitation, quantitative reverse transcription pcr
        anti tag coimmunoprecipitation, primer specific pcr
        anti tag coimmunoprecipitation, northern blot
        anti tag coimmunoprecipitation, quantitative reverse transcription pcr
        anti tag coimmunoprecipitation, northern blot
        anti tag coimmunoprecipitation, quantitative reverse transcription pcr, pull down, Identification by mass spectrometry, western blot
        protein-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation
        anti bait coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry
        pull down, western blot
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        anti tag coimmunoprecipitation, anti tag western blot, western blot
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, Identification by mass spectrometry, western blot
        Alleles Reported to Model Human Disease (Disease Ontology) (3 alleles)
        Models Based on Experimental Evidence ( 3 )
        Modifiers Based on Experimental Evidence ( 0 )
        Allele
        Disease
        Interaction
        References
        Genetic Tools, Stocks and Reagents
        Sources of Stocks
        Contact lab of origin for a reagent not available from a public stock center.
        Bloomington Stock Center Disease Page
        Selected mammalian transgenes
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        amorphic allele - molecular evidence
        P-element activity
        References (4)