Please use this identifier to cite or link to this item:
http://hdl.handle.net/10773/29215
Title: | The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis |
Author: | Ferreira, Mónica Boens, Shannah Winkler, Claudia Szekér, Kathelijne Verbinnen, Iris Van Eynde, Aleyde Fardilha, Margarida Bollen, Mathieu |
Keywords: | Animals Biomarkers Gene deletion Germ cells Immunohistochemistry Intracellular Signaling Peptides and Proteins Male Mammals Mice Mice, knockout Mice, transgenic Protein phosphatase 1 Spermatogenesis |
Issue Date: | 17-Oct-2017 |
Publisher: | Nature Research |
Abstract: | NIPP1 is one of the major nuclear interactors of protein phosphatase PP1. The deletion of NIPP1 in mice is early embryonic lethal, which has precluded functional studies in adult tissues. Hence, we have generated an inducible NIPP1 knockout model using a tamoxifen-inducible Cre recombinase transgene. The inactivation of the NIPP1 encoding alleles (Ppp1r8) in adult mice occurred very efficiently in testis and resulted in a gradual loss of germ cells, culminating in a Sertoli-cell only phenotype. Before the overt development of this phenotype Ppp1r8 -/- testis showed a decreased proliferation and survival capacity of cells of the spermatogenic lineage. A reduced proliferation was also detected after the tamoxifen-induced removal of NIPP1 from cultured testis slices and isolated germ cells enriched for undifferentiated spermatogonia, hinting at a testis-intrinsic defect. Consistent with the observed phenotype, RNA sequencing identified changes in the transcript levels of cell-cycle and apoptosis regulating genes in NIPP1-depleted testis. We conclude that NIPP1 is essential for mammalian spermatogenesis because it is indispensable for the proliferation and survival of progenitor germ cells, including (un)differentiated spermatogonia. |
Peer review: | yes |
URI: | http://hdl.handle.net/10773/29215 |
DOI: | 10.1038/s41598-017-13809-y |
ISSN: | 2045-2322 |
Appears in Collections: | IBIMED - Artigos DCM - Artigos |
Files in This Item:
File | Description | Size | Format | |
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s41598-017-13809-y.pdf | 12.76 MB | Adobe PDF | View/Open |
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