The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/29215 |
Resumo: | 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. |
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The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesisAnimalsBiomarkersGene deletionGerm cellsImmunohistochemistryIntracellular Signaling Peptides and ProteinsMaleMammalsMiceMice, knockoutMice, transgenicProtein phosphatase 1SpermatogenesisNIPP1 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.Nature Research2020-09-14T09:35:31Z2017-10-17T00:00:00Z2017-10-17info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10773/29215eng2045-232210.1038/s41598-017-13809-yFerreira, MónicaBoens, ShannahWinkler, ClaudiaSzekér, KathelijneVerbinnen, IrisVan Eynde, AleydeFardilha, MargaridaBollen, Mathieuinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T11:56:32Zoai:ria.ua.pt:10773/29215Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:01:36.877017Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis |
title |
The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis |
spellingShingle |
The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis Ferreira, Mónica Animals Biomarkers Gene deletion Germ cells Immunohistochemistry Intracellular Signaling Peptides and Proteins Male Mammals Mice Mice, knockout Mice, transgenic Protein phosphatase 1 Spermatogenesis |
title_short |
The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis |
title_full |
The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis |
title_fullStr |
The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis |
title_full_unstemmed |
The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis |
title_sort |
The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis |
author |
Ferreira, Mónica |
author_facet |
Ferreira, Mónica Boens, Shannah Winkler, Claudia Szekér, Kathelijne Verbinnen, Iris Van Eynde, Aleyde Fardilha, Margarida Bollen, Mathieu |
author_role |
author |
author2 |
Boens, Shannah Winkler, Claudia Szekér, Kathelijne Verbinnen, Iris Van Eynde, Aleyde Fardilha, Margarida Bollen, Mathieu |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Ferreira, Mónica Boens, Shannah Winkler, Claudia Szekér, Kathelijne Verbinnen, Iris Van Eynde, Aleyde Fardilha, Margarida Bollen, Mathieu |
dc.subject.por.fl_str_mv |
Animals Biomarkers Gene deletion Germ cells Immunohistochemistry Intracellular Signaling Peptides and Proteins Male Mammals Mice Mice, knockout Mice, transgenic Protein phosphatase 1 Spermatogenesis |
topic |
Animals Biomarkers Gene deletion Germ cells Immunohistochemistry Intracellular Signaling Peptides and Proteins Male Mammals Mice Mice, knockout Mice, transgenic Protein phosphatase 1 Spermatogenesis |
description |
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. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-10-17T00:00:00Z 2017-10-17 2020-09-14T09:35:31Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10773/29215 |
url |
http://hdl.handle.net/10773/29215 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2045-2322 10.1038/s41598-017-13809-y |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Nature Research |
publisher.none.fl_str_mv |
Nature Research |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799137671824539648 |