Disease relevance of Zp3

• A nonamer peptide from murine nicotinic acetylcholine receptor delta chain (ACR delta), which shared four amino acid residues with a nonamer peptide of murine ovarian zona pellucida glycoprotein ZP3, induced murine autoimmune oophoritis and IgG autoantibody to the zona pellucida [1].
• Infertility in mice induced by a recombinant ectromelia virus expressing mouse zona pellucida glycoprotein 3 [2].
• Immunization of female bonnet monkeys (Macaca radiata) with pig zona pellucida glycoprotein ZP3 using adjuvants permissible for human use leads to infertility [3].

High impact information on Zp3

• Four short (8-15 bp) sequences within the first 250 bp of the 5' flanking region in the human Zp-3 homolog are also present upstream of mouse Zp-3 [4].
• During fertilization in mice, zona pellucida glycoprotein ZP3 mediates initial sperm-egg interactions by serving as receptor for sperm [5].
• Galactose at the nonreducing terminus of O-linked oligosaccharides of mouse egg zona pellucida glycoprotein ZP3 is essential for the glycoprotein's sperm receptor activity [5].
• These data are consistent with the hypothesis that common factors binding to conserved element IV are involved in coordinate expression of the oocyte-specific Zp-2 and Zp-3 zona pellucida genes [6].
• Injection of minimal Zp-3 promoter constructs containing element IV in either orientation also resulted in high levels of reporter gene activity, suggesting that the element is not only necessary but also sufficient for expression from zona pellucida promoters [6].

Biological context of Zp3

• It has been previously shown that the integrity of this E-box in Zp2 and Zp3 promoters is required for expression of luciferase reporter genes microinjected into growing oocytes [7].
• An E-box (CANNTG), located approximately 200 bp upstream of the transcription start sites of Zp1, Zp2 and Zp3, forms a protein-DNA complex present in oocytes and, to a much lesser extent, in testes [7].
• The structural defect is more severe than that observed in Zp1-null mice, which have decreased fecundity, but not quite as severe as that observed in Zp3-null mice, which never form a visible zona pellucida and are sterile [8].
• Although zona-free oocytes matured and fertilized in vitro can progress to the blastocyst stage, the developmental potential of blastocysts derived from either Zp2- or Zp3-null eggs appears compromised and, after transfer to foster mothers, live births have not been observed [8].
• We report here that by driving the expression of a transgene encoding an Msy2 hairpin dsRNA in growing oocytes using the oocyte-specific Zp3 promoter, the amount of MSY2 protein was reduced by at least 60% in fully grown oocytes [9].

Anatomical context of Zp3

• Genomic mapping of murine Zp-2 and Zp-3, two oocyte-specific loci encoding zona pellucida proteins [10].
• Lewis X-containing neoglycoproteins mimic the intrinsic ability of zona pellucida glycoprotein ZP3 to induce the acrosome reaction in capacitated mouse sperm [11].
• Recent experiments indicate that the murine zona pellucida glycoprotein ZP3 regulates acrosomal exocytosis by aggregating its corresponding receptors (ZP3-Rs) located in the mouse sperm plasma membrane [12].
• Sperm receptor activity was examined in a competitive gamete binding fashion using the HZA as an indicator of sperm/zona interaction [13].

Associations of Zp3 with chemical compounds

• Fertilization in the mouse is initiated by sperm beta 1,4-galactosyltransferase (GalTase) binding to terminal N-acetylglucosamine residues on the zona pellucida glycoprotein ZP3 [14].

Regulatory relationships of Zp3

• We now define the Zp-2 gene transcript and show that it is coordinately expressed with Zp-3 only during the 2-week growth phase of oogenesis that occurs prior to ovulation [15].

Other interactions of Zp3

• The Gal alpha 1-->3Gal structure is displayed on the zona pellucida glycoprotein ZP3 on murine oocytes [16].
• The oocyte-specific Zp3 promoter was used to drive the expression of a long hairpin dsRNA ( approximately 500 bp) targeting Mos mRNA [17].
• The expression of iCre of GDF-9-iCre mice was shown to be earlier than the Cre expression of Zp3Cre and Msx2Cre mice, in which the Cre gene is driven by zona pellucida protein 3 (Zp3) promoter and a homeobox gene Msx2 promoter, respectively, in the postnatal ovary [18].

Analytical, diagnostic and therapeutic context of Zp3

• Mutation of these five elements (I, IIA, IIB, III, and IV) in Zp-luciferase constructs demonstrates that the 12-bp element IV, positioned approximately 200 bp upstream from the TATAA box, is necessary for high-level expression from the mouse Zp-2 and Zp-3 promoters after microinjection into the nuclei of 50-microns-diameter oocytes [6].
• Oligonucleotides containing the conserved element from either Zp-2 or Zp-3 form DNA-protein complexes of identical mobility in gel retardation assays using extracts of oocytes but not other tissues [6].

References