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Mice homozygous for an insertional mutation in the Zp3 gene lack a zona pellucida and are infertile.
- Source :
-
Development (Cambridge, England) [Development] 1996 Sep; Vol. 122 (9), pp. 2903-10. - Publication Year :
- 1996
-
Abstract
- Mammalian oocytes synthesize and secrete a zona pellucida that surrounds the growing oocytes, ovulated eggs and preimplantation embryos. The extracellular zona matrix is composed of three glycoproteins (ZP1, ZP2, ZP3) that are involved in folliculogenesis, species-specific fertilization, and passage of the early embryo down the oviduct. We have established a mouse line in which Zp3 has been inactivated by homologous recombination with an insertional mutation. Neither Zp3 transcripts nor ZP3 protein was detected in female mice homozygous for the mutation (Zp3-/-), whereas both ZP1 and ZP2 were present in mutant oocytes. Homozygous mutant Zp3-/- mice had follicles with germinal-vesicle-intact oocytes but that lacked a zona pellucida matrix and had a disorganized corona radiata. Although mutant oocytes underwent germinal vesicle breakdown (GVBD) prior to ovulation, the cumulus-oocyte complex was markedly disrupted and the oocytes were often separate from the cumulus cells. After hormone-induced ovulation, cumulus masses were present in the oviducts of homozygous mutant mice, but zona-free eggs were observed in only half of the females and, in these, less than 10% of the normal number [correction of mumber] of eggs were detected. No zona-free 2-cell embryos were recovered from homozygous mutant Zp3-/- female mice after mating with males proven to be fertile, and none became visibly pregnant or produced offspring. These results demonstrate that a genetic defect in a zona pellucida gene causes infertility and, given the conserved nature of the zona pellucida, a similar phenotype is expected in other mammals.
- Subjects :
- Animals
Blotting, Southern
Egg Proteins metabolism
Female
Gene Targeting
Genotype
Homozygote
Immunohistochemistry
In Situ Hybridization
Infertility, Female pathology
Male
Membrane Glycoproteins metabolism
Mice
Mice, Transgenic
Microscopy, Confocal
Mutagenesis, Insertional
Oocytes chemistry
Ovary pathology
Ovulation
RNA, Antisense genetics
RNA, Antisense metabolism
Zona Pellucida Glycoproteins
Egg Proteins genetics
Infertility, Female etiology
Membrane Glycoproteins genetics
Oocytes metabolism
Receptors, Cell Surface
Zona Pellucida metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0950-1991
- Volume :
- 122
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 8787763
- Full Text :
- https://doi.org/10.1242/dev.122.9.2903