CRISPR/Cas9-based genome editing in mice uncovers 13 testis- or epididymis-enriched genes individually dispensable for male reproduction

Developing a safe and effective male contraceptive remains a challenge in the field of medical science. Molecules that selectively target the male reproductive tract and whose targets are indispensable for male reproductive function serve among the best candidates for a novel non-hormonal male contr...

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Bibliographic Details
Published in:Biology of reproduction 2020-08, Vol.103 (2), p.183-194
Main Authors: Sun, Jiang, Lu, Yonggang, Nozawa, Kaori, Xu, Zoulan, Morohoshi, Akane, Castaneda, Julio M, Noda, Taichi, Miyata, Haruhiko, Abbasi, Ferheen, Shawki, Hossam H, Takahashi, Satoru, Devlin, Darius J, Yu, Zhifeng, Matzuk, Ryan M, Garcia, Thomas X, Matzuk, Martin M, Ikawa, Masahito
Format: Article
Language:English
Subjects:
CONTRACEPTIVE SPECIAL ISSUE
CRISPR
CRISPR/Cas9
epididymis
Genetic aspects
Genetic engineering
Genome editing
knockout mice
male contraceptive
male infertility
Males
Methods
Sperm
Testis
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Summary:Developing a safe and effective male contraceptive remains a challenge in the field of medical science. Molecules that selectively target the male reproductive tract and whose targets are indispensable for male reproductive function serve among the best candidates for a novel non-hormonal male contraceptive method. To determine the function of these genes in vivo, mutant mice carrying disrupted testis- or epididymis-enriched genes were generated by zygote microinjection or electroporation of the CRISPR/Cas9 components. Male fecundity was determined by consecutively pairing knockout males with wild-type females and comparing the fecundity of wild-type controls. Phenotypic analyses of testis appearance and weight, testis and epididymis histology, and sperm movement were further carried out to examine any potential spermatogenic or sperm maturation defect in mutant males. In this study, we uncovered 13 testis- or epididymis-enriched evolutionarily conserved genes that are individually dispensable for male fertility in mice. Owing to their dispensable nature, it is not feasible to use these targets for the development of a male contraceptive. Summary sentence Thirteen testis- or epididymis-enriched genes are individually dispensable for male fertility based on phenotypic analyses of mutant mice produced by the CRISPR/Cas9 system.
ISSN:0006-3363
1529-7268
DOI:10.1093/biolre/ioaa083