Disease relevance of DAZL

• Y-chromosomal DAZ (deleted in azoospermia) and autosomal DAZ-like (DAZL) comprise a gene family involved in gametogenesis [1].
• CONCLUSION: In a selected Caucasian population, the DAZL SNP 386 is completely absent and SNP 260 is not associated with spermatogenic failure and therefore does not represent a molecular marker for genetic diagnosis of male infertility [2].
• CONCLUSIONS: These observations suggest that seminoma and breast carcinoma express a common stem cell profile and that the expression of DAZL and VASA in seminoma mark the germ cell origin of seminoma that is absent in breast carcinoma [3].
• Characterization of the mouse Dazap1 gene encoding an RNA-binding protein that interacts with infertility factors DAZ and DAZL [4].
• Our results demonstrate high similarity between the human DAZL1 and the mouse Dazl1 gene expression patterns during embryonic development, suggesting that the human gene functions at the first phase of gametogenesis, just as in the mouse, where Dazl1 mutations cause male and female sterility [5].

High impact information on DAZL

• The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis [6].
• Pum2 also interacts with the Xenopus homolog of human Deleted for Azoospermia-like (DAZL) and the embryonic poly(A)-binding protein (ePAB) [7].
• In the present study, we investigated the cellular functions of Dazl in the mouse male germ cells [8].
• In order to directly address the function of vertebrate DAZL proteins, we have used Xenopus laevis oocytes as a model system [9].
• Germ-line transmission of the transgene occurred, and its expression correlated with significant reductions in DAZL protein levels and male sterility, and the knockdown was stable over multiple generations (F(1)-F(3)) [10].

Biological context of DAZL

• DAZL proteins are germ-cell-specific RNA-binding proteins essential for gametogenesis [9].
• Our findings provide strong evidence for the role of the autosomal DAZL gene in human spermatogenesis [11].
• Here, we report identification and characterization of RNA sequences to which PUM2 and DAZL bind [12].
• No association of the A260G and A386G DAZL single nucleotide polymorphisms with male infertility in a Caucasian population [2].
• These findings confirm that DAZL and DAZ can only substitute for early functions of the murine homologue resulting in the establishment of the germ cell population and partial progression into meiosis [1].

Anatomical context of DAZL

• This leads to an attractive hypothesis whereby DAZL proteins activate translationally silent mRNAs during germ cell development through the direct recruitment of PABPs [9].
• SPGYLA encodes an RNA binding protein expressed only in the human male gonad [13].
• Further observations using human tissues indicate that, unlike DAZ, human DAZL protein persists in spermatids and even spermatozoa [14].
• Expression patterns and transcript concentrations of the autosomal DAZL gene in testes of azoospermic men [15].
• In blastocysts, DAZL transcripts were only detected in those of good quality and this as well in the inner cell mass (ICM) as in the trophectoderm (TE) [16].

Associations of DAZL with chemical compounds

• Expression of DAZL protein in the human corpus luteum [17].
• Cell-specific immunohistochemistry and confocal microscopy were used to track development of Sertoli [anti-Müllerian hormone (AMH), Wilm's tumour (WT-1) protein, p27(kip)], Leydig [3beta-hydroxysteroid dehydrogenase (3beta-HSD)], germ (DAZL protein) and peritubular myoid (smooth muscle actin) cells from fetal life to adulthood [18].
• A number of molecules are involved in this differentiation step including the stem cell factor-c-kit system, the Dazl RNA binding protein, cyclin D(2) and retinoic acid [19].

Enzymatic interactions of DAZL

• Identification and characterization of RNA sequences to which human PUMILIO-2 (PUM2) and deleted in Azoospermia-like (DAZL) bind [12].

Other interactions of DAZL

• We also show that PUM2 is expressed predominantly in human embryonic stem cells and germ cells and colocalizes with DAZ and DAZL in germ cells [20].
• We confirmed that the interacting proteins, PUM2 and DAZL, are capable of binding the same RNA target and further characterized mRNA sequences bound by both proteins in the 3'UTR of human SDAD1 mRNA [12].
• Evolutionary comparison of the reproductive genes, DAZL and BOULE, in primates with and without DAZ [21].
• CONCLUSION(S): The expression patterns of DAZAP1 and DAZL are identical within rat and human ovaries [22].
• Recently a polymorphism in the deleted in azoospermia-like (DAZL) gene (T54A) was reported as susceptibility factor to oligo/azoospermia in the Chinese population [23].

Analytical, diagnostic and therapeutic context of DAZL

• Although the sample size is limited, no compensatory increase of DAZL or BOULE transcription was found in men with DAZ deletion [24].
• INTERVENTION(S): Reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunostaining for DAZL [25].
• Co-immunoprecipitation experiments show in vivo interaction of DAZ-like (DAZL) protein with DAZAP1 in the ovarian tissues [22].
• Using a panel of rodent-human somatic cell lines and fluorescence in situ hybridization, the DAZLA gene was mapped to 3p24, a region not known to share homology with mouse chromosome 17 [26].
• INTERVENTION(S): Single strand conformation polymorphism and sequence analysis for DAZL gene polymorphism screening were done for all subjects enrolled [27].

References