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Updated: Jul 13, 2026

Zygote Microinjection for Creating Gene Cassette Knock-in and Flox Alleles in Mice
Published on: June 24, 2022
Sperm-egg interaction and gene manipulated animals
Naokazu Inoue1, Ryo Yamaguchi, Masahito Ikawa
1Genome Information Research Center, Osaka University, Yamadaoka 3-1, Suita, Osaka 565-0871, Japan.
Abstract:
It is intriguing that the disruption of a number of genes, e.g., Clgn, Ace, Adamla, Adam2 and Adam3 results in a similar sperm phenotype, i.e., failure of sperm to bind to the zona pellucida (ZP). Because calmegin functions as a testis-specific molecular chaperone, there is a possibility of misfolding of ADAMs in sperm from Clgn-/- mice. In the first half of this review we describe the interaction of ADAMs with calmegin and try to elucidate the relationship of these proteins to establish the zona binding ability. In the second half of this review we describe other gene manipulated animals that lead to a defect in sperm-egg fusion. The first factor, CD9, was found serendipitously on the egg side, while the second factor, Izumo, on the sperm side, was discovered after 20 years of pursuit. Here we describe various gene manipulated animals that are useful to elucidate the mechanism of fertilisation.
Insights
Disruptions in genes like Clgn, Ace, Adamla, Adam2, and Adam3 cause sperm to fail zona pellucida binding. This review explores calmegin
Area of Science:
- Reproductive Biology
- Molecular Biology
- Genetics
Background:
- Specific gene disruptions (Clgn, Ace, Adamla, Adam2, Adam3) lead to a shared sperm phenotype: failure to bind the zona pellucida (ZP).
- Calmegin (Clgn) acts as a testis-specific molecular chaperone, suggesting potential misfolding of ADAM proteins in Clgn-deficient sperm.
Purpose of the Study:
- To elucidate the relationship between calmegin and ADAM proteins in establishing sperm zona binding ability.
- To review gene-manipulated animal models that exhibit defects in sperm-egg fusion.
Main Methods:
- Review of existing literature on gene disruptions affecting sperm function.
- Analysis of the interaction between calmegin and ADAM proteins.
- Examination of gene-manipulated animal models relevant to fertilization.
Main Results:
- Evidence suggests a link between calmegin function and the proper folding/function of ADAM proteins, impacting zona pellucida binding.
- Other factors involved in sperm-egg fusion, such as CD9 (egg side) and Izumo (sperm side), have been identified.
Conclusions:
- Understanding the roles of calmegin, ADAMs, CD9, and Izumo is crucial for elucidating fertilization mechanisms.
- Gene-manipulated animals provide valuable models for studying these complex processes.
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