Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/95571
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Type: Journal article
Title: Loss of GGN leads to pre-implantation embryonic lethality and compromised male meiotic DNA double strand break repair in the mouse
Author: Jamsai, D.
O'Connor, A.
DeBoer, K.
Clark, B.
Smith, S.
Browne, C.
Bensley, J.
Merriman, J.
Yuen, W.
Koopman, P.
Jones, K.
O'Bryan, M.
Citation: PLoS One, 2013; 8(2):e56955-1-e56955-7
Publisher: Public Library of Science
Issue Date: 2013
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
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
Abstract: 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.
Keywords: DNA Repair
Rights: © 2013 Jamsai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0030036141
DOI: 10.1371/journal.pone.0056955
Grant ID: http://purl.org/au-research/grants/nhmrc/143786
http://purl.org/au-research/grants/arc/CE0348239
http://purl.org/au-research/grants/arc/DP110102288
http://purl.org/au-research/grants/nhmrc/384297
http://purl.org/au-research/grants/nhmrc/384132
Appears in Collections:Medicine publications

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