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A novel gene mutation in ZP3 loop region identified in patients with empty follicle syndrome
- Source :
- Human Mutation. 43:180-188
- Publication Year :
- 2021
- Publisher :
- Hindawi Limited, 2021.
-
Abstract
- The zona pellucida (ZP) is an extracellular matrix surrounding mammalian oocytes. It is composed of three to four glycoproteins, ZP1-ZP4. ZP3 is essential for sperm binding and zona matrix formation. Here, we identified a novel heterozygous mutation (NM_001110354.2:c.502_504delGAG) of ZP3, occurring in a pair of sisters with empty follicle syndrome (EFS). A mouse model with the same mutation was established using the CRISPR/Cas9 gene-editing system. As in the above family, F0 -, F1 -, and F2 -generation female mice with the mutation were all infertile. Further analysis using the Chinese hamster ovary cells (CHO-K1) also showed that this mutation weakens the strength of binding between ZP3 and ZP2, which hinders the assembly of ZP and results in unstable ZP formation. Immunohistochemical analysis using ovarian serial sections in both humans and mice demonstrated that the ZP of preantral follicles was thinner than normal control, or even absent. Our study presents a new gene mutation that leads to EFS, providing new evidence and support for the genetic diagnosis of infertile individuals with similar phenotypes. Our results also show that the loop of ZP3 is not only a linker between two amphiphilic helices but may play a critical role in specifying the correct heterodimerization partner. This article is protected by copyright. All rights reserved.
- Subjects :
- CHO Cells
Gene mutation
Matrix (biology)
Biology
Zona Pellucida Glycoproteins
Extracellular matrix
Mice
Cricetulus
Cricetinae
Genetics
medicine
Animals
Humans
Ovarian Diseases
Zona pellucida
Zona Pellucida
Genetics (clinical)
chemistry.chemical_classification
Chinese hamster ovary cell
Phenotype
Cell biology
medicine.anatomical_structure
chemistry
Mutation
Mutation (genetic algorithm)
Oocytes
Female
Glycoprotein
Subjects
Details
- ISSN :
- 10981004 and 10597794
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- Human Mutation
- Accession number :
- edsair.doi.dedup.....1d87662306b3dd79e9e38c8577f65601