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Biol Reprod. 2019 Jun 14. pii: ioz103. doi: 10.1093/biolre/ioz103. [Epub ahead of print]

CRISPR/Cas9-mediated genome editing reveals 30 testis-enriched genes dispensable for male fertility in mice.

Author information

1
Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871, Japan.
2
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 5650871, Japan.
3
RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 6500047, Japan.
4
Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center, Suita, Osaka 5658565, Japan.
5
Graduate School of Medicine, Osaka University, Suita, Osaka 5650871, Japan.
6
Immunology Frontier Research Center, Osaka University, Osaka 5650871, Japan.
7
Laboratory Animal Center, Chongqing Medical University, Chongqing 400016, China.
8
Priority Research Centre for Reproductive Science, Faculty of Science, The University of Newcastle, Callaghan, NSW 2308, Australia.
9
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030.
10
Center for Drug Discovery, Baylor College of Medicine, Houston, TX 77030.
11
Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030.
12
Advanced Technology Cores, Baylor College of Medicine, Houston, TX, 77030.
13
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030.
14
Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara 6300192, Japan.
15
Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
16
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030.
17
Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030.
18
Department of Biology and Biotechnology, University of Houston-Clear Lake, Houston, TX 77058.
19
The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan.

Abstract

More than 1,000 genes are predicted to be predominantly expressed in mouse testis, yet many of them remain unstudied in terms of their roles in spermatogenesis and sperm function and their essentiality in male reproduction. Since individually indispensable factors can provide important implications for the diagnosis of genetically-related idiopathic male infertility and may serve as candidate targets for the development of non-hormonal male contraceptives, our laboratories continuously analyze the functions of testis-enriched genes in vivo by generating knockout mouse lines using the CRISPR/Cas9 system. The dispensability of genes in male reproduction is easily determined by examining the fecundity of knockout males. During our large-scale screening of essential factors, we knocked out 30 genes that have a strong bias of expression in the testis and are mostly conserved in mammalian species including human. Fertility tests reveal that the mutant males exhibited normal fecundity, suggesting these genes are individually dispensable for male reproduction. Since such functionally redundant genes are of diminished biological and clinical significance, we believe that it is crucial to disseminate this list of genes, along with their phenotypic information, to the scientific community to avoid unnecessary expenditure of time and research funds and duplication of efforts by other laboratories.

KEYWORDS:

CRISPR/Cas9; knockout mice; male infertility; spermatogenesis; testis expression

PMID:
31201419
DOI:
10.1093/biolre/ioz103

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