Loss of GGN Leads to Pre-Implantation Embryonic Lethality and Compromised Male Meiotic DNA Double Strand Break Repair in the Mouse

Jamsai, Duangporn, O'Connor, Anne E., DeBoer, Kathleen D., Clark, Brett J., Smith, Stephanie J., Browne, Catherine M., Bensley, Jonathan G., Merriman, Julie A., Yuen, Wai Shan, Koopman, Peter, Jones, Keith T. and O'Bryan, Moira K. (2013) Loss of GGN Leads to Pre-Implantation Embryonic Lethality and Compromised Male Meiotic DNA Double Strand Break Repair in the Mouse. PLoS One, 8 2: e56955.1-e56955.7. doi:10.1371/journal.pone.0056955


Author Jamsai, Duangporn
O'Connor, Anne E.
DeBoer, Kathleen D.
Clark, Brett J.
Smith, Stephanie J.
Browne, Catherine M.
Bensley, Jonathan G.
Merriman, Julie A.
Yuen, Wai Shan
Koopman, Peter
Jones, Keith T.
O'Bryan, Moira K.
Title Loss of GGN Leads to Pre-Implantation Embryonic Lethality and Compromised Male Meiotic DNA Double Strand Break Repair in the Mouse
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-02
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0056955
Open Access Status DOI
Volume 8
Issue 2
Start page e56955.1
End page e56955.7
Total pages 7
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2014
Language eng
Formatted 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.
Keyword Fanconi anemia
Targeted Disruption
Gene Leads
Mice
Pathway
Fertility
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
Institute for Molecular Bioscience - Publications
 
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