New allele of mouse DNA/RNA helicase senataxin causes meiotic arrest and infertility

in Reproduction
Authors:
Yasuhiro Fujiwara Institute of Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan
The Jackson Laboratory, Bar Harbor, Maine, USA

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https://orcid.org/0000-0002-6416-9679
,
Kouhei Saito Institute of Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan

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Fengyun Sun The Jackson Laboratory, Bar Harbor, Maine, USA
Biochemistry and Molecular Pharmacology Department, University of Massachusetts Medical School, Worcester, Massachusetts, USA

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Sabrina Petri The Jackson Laboratory, Bar Harbor, Maine, USA

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Erina Inoue Institute of Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan

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John Schimenti Department of Biological Sciences, Center for Vertebrate Genomics, Cornell University College of Veterinary Medicine, Ithaca, New York, USA

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Yuki Okada Institute of Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan

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Mary Ann Handel The Jackson Laboratory, Bar Harbor, Maine, USA

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Correspondence should be addressed to Y Fujiwara; Email: y.fujiwara@iqb.u-tokyo.ac.jp
DOI:
https://doi.org/10.1530/REP-23-0166
Volume/Issue:
Volume 166: Issue 6
Page Range:
437–450
Article Type:
Research Article
Online Publication Date:
06 Nov 2023
Copyright:
© Society for Reproduction and Fertility 2023
Restricted access
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In brief

A new allele of the senataxin gene Setxspcar3 causes meiotic arrest of spermatocytes with aberrant DNA damage and accumulation of R-loops.

Abstract

An unbiased screen for discovering novel mouse genes for fertility identified the spcar3, spermatocyte arrest 3, mutant phenotype. The spcar3 mutation identified a new allele of the Setx gene, encoding senataxin, a DNA/RNA helicase that regulates transcription termination by resolving DNA/RNA hybrid R-loop structures. The Setxspcar3 mutant mice exhibit male infertility and female subfertility. Histology of the Setxspcar3 mutant testes revealed the absence of spermatids and mature spermatozoa in the seminiferous tubules. Cytological analysis of chromosome preparations of the Setxspcar3 mutant spermatocytes revealed normal synapsis, but aberrant DNA damage in the autosomes, defective formation of the sex body, and arrest of meiosis in mid-prophase. Additionally, Setxspcar3 testicular cells exhibit abnormal accumulation of R-loops. Transient expression assays identified regions of the senataxin protein required for sub-nuclear localization. Together, these results not only confirm that senataxin is required for normal meiosis and spermatogenesis but also provide a new resource for the determination of its role in maintaining R-loop formation and genome integrity.

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Print ISSN:
1470-1626
Online ISSN:
1741-7899

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