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Int. J. Mol. Sci. 2017, 18(10), 2208; https://doi.org/10.3390/ijms18102208

Human Globozoospermia-Related Gene Spata16 Is Required for Sperm Formation Revealed by CRISPR/Cas9-Mediated Mouse Models

1
Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
2
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan
3
RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan
4
School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan
5
Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
6
The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
*
Author to whom correspondence should be addressed.
Received: 26 September 2017 / Revised: 19 October 2017 / Accepted: 19 October 2017 / Published: 21 October 2017
(This article belongs to the Special Issue Genome Editing 2018)
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Abstract

A recent genetic analysis of infertile globozoospermic patients identified causative mutations in three genes: a protein interacting with C kinase 1 (PICK1), dpy 19-like 2 (DPY19L2), and spermatogenesis associated 16 (SPATA16). Although mouse models have clarified the physiological functions of Pick1 and Dpy19l2 during spermatogenesis, Spata16 remains to be determined. Globozoospermic patients carried a homozygous point mutation in SPATA16 at 848G→A/R283Q. We generated CRISPR/Cas9-mediated mutant mice with the same amino acid substitution in the fourth exon of Spata16 to analyze the mutation site at R284Q, which corresponded with R283Q of mutated human SPATA16. We found that the point mutation in Spata16 was not essential for male fertility; however, deletion of the fourth exon of Spata16 resulted in infertile male mice due to spermiogenic arrest but not globozoospermia. This study demonstrates that Spata16 is indispensable for male fertility in mice, as well as in humans, as revealed by CRISPR/Cas9-mediated mouse models. View Full-Text
Keywords: genome editing; male infertility; mouse model; point mutation; spermatogenesis; testis genome editing; male infertility; mouse model; point mutation; spermatogenesis; testis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Fujihara, Y.; Oji, A.; Larasati, T.; Kojima-Kita, K.; Ikawa, M. Human Globozoospermia-Related Gene Spata16 Is Required for Sperm Formation Revealed by CRISPR/Cas9-Mediated Mouse Models. Int. J. Mol. Sci. 2017, 18, 2208.

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