Journal article
Conditional inactivation of Miwi2 reveals that MIWI2 is only essential for prospermatogonial development in mice
Cell death and differentiation, Vol.21(5), pp.783-796
05/2014
Handle:
https://hdl.handle.net/2376/114404
PMCID: PMC3978311
PMID: 24464225
Abstract
The PIWI-piRNA pathway serves as a critical defense mechanism through which the genome of the male germline is protected from invasion by transposable elements (TEs). MIWI2/PIWIL4, a member of the murine PIWI subclade of the Argonaute family, has been shown to be expressed in primordial germ cells (PGCs) and prospermatogonia in fetal and prepubertal testes. Global inactivation of Miwi2 leads to male sterility due to an early meiotic arrest, which correlates with retrotransposon desuppression. However, it remains unclear whether MIWI2 functions beyond the PGC stage and whether MIWI2 has a role beyond TE suppression during male germ line development. Through conditional inactivation of Miwi2, we demonstrate herein that MIWI2 function is restricted to a narrow time window during male PGC reprograming and that Miwi2 is dispensable for postnatal male germline development and testicular function in mice. Moreover, persistent activation of LINE1 and IAP retrotransposons caused by Miwi2 inactivation is compatible with mitotic cell cycle progression of spermatogonia during the first wave of spermatogenesis, but can cause zygotene to pachytene arrest in early meiosis due to multiple defects including enhanced DNA double-strand breaks, aberrant histone modifications and altered mRNA transcriptome. Our data not only validate those from global Miwi2 KO studies, but also suggest that MIWI2 and MIWI2-associated piRNAs have functions beyond TE suppression.
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Details
- Title
- Conditional inactivation of Miwi2 reveals that MIWI2 is only essential for prospermatogonial development in mice
- Creators
- J Bao - Department of Physiology and Cell Biology, University of Nevada Reno School of Medicine, 1664 North Virginia Street, Mailstop 0575, Reno, NV 89557, USAY Zhang - Department of Physiology and Cell Biology, University of Nevada Reno School of Medicine, 1664 North Virginia Street, Mailstop 0575, Reno, NV 89557, USAA S Schuster - Department of Physiology and Cell Biology, University of Nevada Reno School of Medicine, 1664 North Virginia Street, Mailstop 0575, Reno, NV 89557, USAN Ortogero - Department of Physiology and Cell Biology, University of Nevada Reno School of Medicine, 1664 North Virginia Street, Mailstop 0575, Reno, NV 89557, USAE E Nilsson - Washington State University, Abelson Hall Room 507, Pullman, WA 99164, USAM K Skinner - Washington State University, Abelson Hall Room 507, Pullman, WA 99164, USAW Yan - Department of Physiology and Cell Biology, University of Nevada Reno School of Medicine, 1664 North Virginia Street, Mailstop 0575, Reno, NV 89557, USA
- Publication Details
- Cell death and differentiation, Vol.21(5), pp.783-796
- Academic Unit
- Biological Sciences, School of
- Publisher
- England
- Grant note
- P20 RR018751 / NCRR NIH HHS R03 HD074573 / NICHD NIH HHS R01 HD060858 / NICHD NIH HHS HD071736 / NICHD NIH HHS R21 HD071736 / NICHD NIH HHS HD060858 / NICHD NIH HHS R01 ES012974 / NIEHS NIH HHS HD074573 / NICHD NIH HHS P20-RR18751 / NCRR NIH HHS
- Identifiers
- 99900547443401842
- Language
- English
- Resource Type
- Journal article