Loss of GGN leads to pre-implantation embryonic lethality and compromised male meiotic DNA double strand break repair in the mouse.

The integrity of male germ cell genome is critical for the correct progression of spermatogenesis, successful fertilization, and proper development of the offspring. Several DNA repair pathways exist in male germ cells. However, unlike somatic cells, key components of such pathways remain largely un...

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Autores principales:	Duangporn Jamsai, Anne E O'Connor, Kathleen D Deboer, Brett J Clark, Stephanie J Smith, Catherine M Browne, Jonathan G Bensley, Julie A Merriman, Wai Shan Yuen, Peter Koopman, Keith T Jones, Moira K O'Bryan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d7a0f0a865394e3486e2c03857a7f8d2
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spelling	oai:doaj.org-article:d7a0f0a865394e3486e2c03857a7f8d22021-11-18T07:56:22ZLoss of GGN leads to pre-implantation embryonic lethality and compromised male meiotic DNA double strand break repair in the mouse.1932-620310.1371/journal.pone.0056955https://doaj.org/article/d7a0f0a865394e3486e2c03857a7f8d22013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23451117/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The integrity of male germ cell genome is critical for the correct progression of spermatogenesis, successful fertilization, and proper development of the offspring. Several DNA repair pathways exist in male germ cells. However, unlike somatic cells, key components of such pathways remain largely unidentified. Gametogenetin (GGN) is a testis-enriched protein that has been shown to bind to the DNA repair protein FANCL via yeast-two-hybrid assays. This finding and its testis-enriched expression pattern raise the possibility that GGN plays a role in DNA repair during spermatogenesis. Herein we demonstrated that the largest isoform GGN1 interacted with components of DNA repair machinery in the mouse testis. In addition to FANCL, GGN1 interacted with the critical component of the Fanconi Anemia (FA) pathway FANCD2 and a downstream component of the BRCA pathway, BRCC36. To define the physiological function of GGN, we generated a Ggn null mouse line. A complete loss of GGN resulted in embryonic lethality at the very earliest period of pre-implantation development, with no viable blastocysts observed. This finding was consistent with the observation that Ggn mRNA was also expressed in lower levels in the oocyte and pre-implantation embryos. Moreover, pachytene spermatocytes of the Ggn heterozygous knockout mice showed an increased incidence of unrepaired DNA double strand breaks (DSBs). Together, our results suggest that GGN plays a role in male meiotic DSB repair and is absolutely required for the survival of pre-implantation embryos.Duangporn JamsaiAnne E O'ConnorKathleen D DeboerBrett J ClarkStephanie J SmithCatherine M BrowneJonathan G BensleyJulie A MerrimanWai Shan YuenPeter KoopmanKeith T JonesMoira K O'BryanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e56955 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Duangporn Jamsai Anne E O'Connor Kathleen D Deboer Brett J Clark Stephanie J Smith Catherine M Browne Jonathan G Bensley Julie A Merriman Wai Shan Yuen Peter Koopman Keith T Jones Moira K O'Bryan Loss of GGN leads to pre-implantation embryonic lethality and compromised male meiotic DNA double strand break repair in the mouse.
description	The integrity of male germ cell genome is critical for the correct progression of spermatogenesis, successful fertilization, and proper development of the offspring. Several DNA repair pathways exist in male germ cells. However, unlike somatic cells, key components of such pathways remain largely unidentified. Gametogenetin (GGN) is a testis-enriched protein that has been shown to bind to the DNA repair protein FANCL via yeast-two-hybrid assays. This finding and its testis-enriched expression pattern raise the possibility that GGN plays a role in DNA repair during spermatogenesis. Herein we demonstrated that the largest isoform GGN1 interacted with components of DNA repair machinery in the mouse testis. In addition to FANCL, GGN1 interacted with the critical component of the Fanconi Anemia (FA) pathway FANCD2 and a downstream component of the BRCA pathway, BRCC36. To define the physiological function of GGN, we generated a Ggn null mouse line. A complete loss of GGN resulted in embryonic lethality at the very earliest period of pre-implantation development, with no viable blastocysts observed. This finding was consistent with the observation that Ggn mRNA was also expressed in lower levels in the oocyte and pre-implantation embryos. Moreover, pachytene spermatocytes of the Ggn heterozygous knockout mice showed an increased incidence of unrepaired DNA double strand breaks (DSBs). Together, our results suggest that GGN plays a role in male meiotic DSB repair and is absolutely required for the survival of pre-implantation embryos.
format	article
author	Duangporn Jamsai Anne E O'Connor Kathleen D Deboer Brett J Clark Stephanie J Smith Catherine M Browne Jonathan G Bensley Julie A Merriman Wai Shan Yuen Peter Koopman Keith T Jones Moira K O'Bryan
author_facet	Duangporn Jamsai Anne E O'Connor Kathleen D Deboer Brett J Clark Stephanie J Smith Catherine M Browne Jonathan G Bensley Julie A Merriman Wai Shan Yuen Peter Koopman Keith T Jones Moira K O'Bryan
author_sort	Duangporn Jamsai
title	Loss of GGN leads to pre-implantation embryonic lethality and compromised male meiotic DNA double strand break repair in the mouse.
title_short	Loss of GGN leads to pre-implantation embryonic lethality and compromised male meiotic DNA double strand break repair in the mouse.
title_full	Loss of GGN leads to pre-implantation embryonic lethality and compromised male meiotic DNA double strand break repair in the mouse.
title_fullStr	Loss of GGN leads to pre-implantation embryonic lethality and compromised male meiotic DNA double strand break repair in the mouse.
title_full_unstemmed	Loss of GGN leads to pre-implantation embryonic lethality and compromised male meiotic DNA double strand break repair in the mouse.
title_sort	loss of ggn leads to pre-implantation embryonic lethality and compromised male meiotic dna double strand break repair in the mouse.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/d7a0f0a865394e3486e2c03857a7f8d2
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Loss of GGN leads to pre-implantation embryonic lethality and compromised male meiotic DNA double strand break repair in the mouse.

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