Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/95601
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Type: Journal article
Title: A missense mutation in the transcription factor ETV5 leads to sterility, increased embryonic and perinatal death, postnatal growth restriction, renal asymmetry and polydactyly in the mouse
Author: Jamsai, D.
Clark, B.
Smith, S.
Whittle, B.
Goodnow, C.
Ormandy, C.
O'Bryan, M.
Citation: PLoS One, 2013; 8(10):e77311-1-e77311-8
Publisher: Public Library of Science
Issue Date: 2013
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Duangporn Jamsai, Brett J. Clark, Stephanie J. Smith, Belinda Whittle, Christopher C. Goodnow, Christopher J. Ormandy, Moira K. O'Bryan
Abstract: ETV5 (Ets variant gene 5) is a transcription factor that is required for fertility. In this study, we demonstrate that ETV5 plays additional roles in embryonic and postnatal developmental processes in the mouse. Through a genome-wide mouse mutagenesis approach, we generated a sterile mouse line that carried a nonsense mutation in exon 12 of the Etv5 gene. The mutation led to the conversion of lysine at position 412 into a premature termination codon (PTC) within the ETS DNA binding domain of the protein. We showed that the PTC-containing allele produced a highly unstable mRNA, which in turn resulted in an undetectable level of ETV5 protein. The Etv5 mutation resulted in male and female sterility as determined by breeding experiments. Mutant males were sterile due to a progressive loss of spermatogonia, which ultimately resulted in a Sertoli cell only phenotype by 8 week-of-age. Further, the ETV5 target genes Cxcr4 and Ccl9 were significantly down-regulated in mutant neonate testes. CXCR4 and CCL9 have been implicated in the maintenance and migration of spermatogonia, respectively. Moreover, the Etv5 mutation resulted in several developmental abnormalities including an increased incidence of embryonic and perinatal lethality, postnatal growth restriction, polydactyly and renal asymmetry. Thus, our data define a physiological role for ETV5 in many aspects of development including embryonic and perinatal survival, postnatal growth, limb patterning, kidney development and fertility.
Keywords: Spermatogonia; Mice, Transgenic
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: 0030036137
DOI: 10.1371/journal.pone.0077311
Grant ID: http://purl.org/au-research/grants/nhmrc/384297
http://purl.org/au-research/grants/nhmrc/545805
http://purl.org/au-research/grants/nhmrc/481310
Appears in Collections:Medicine publications

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