Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/120801
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Type: | Journal article |
Title: | A mutation in the viral sensor 2’-5’-oligoadenylate synthetase 2 causes failure of lactation |
Author: | Oakes, S.R. Gallego-Ortega, D. Stanford, P.M. Junankar, S. Au, W.W.Y. Kikhtyak, Z. von Korff, A. Sergio, C.M. Law, A.M.K. Castillo, L.E. Allerdice, S.L. Young, A.I.J. Piggin, C. Whittle, B. Bertram, E. Naylor, M.J. Roden, D.L. Donovan, J. Korennykh, A. Goodnow, C.C. et al. |
Citation: | PLoS Genetics, 2017; 13(11):e1007072-1-e1007072-24 |
Publisher: | Public Library Science |
Issue Date: | 2017 |
ISSN: | 1553-7390 1553-7404 |
Editor: | Wells, C.A. |
Statement of Responsibility: | Samantha R. Oakes, David Gallego-Ortega, Prudence M. Stanford, Simon Junankar, Wendy Wing Yee Au ... Moira K. O’Bryan ... et al. |
Abstract: | We identified a non-synonymous mutation in Oas2 (I405N), a sensor of viral double-stranded RNA, from an ENU-mutagenesis screen designed to discover new genes involved in mammary development. The mutation caused post-partum failure of lactation in healthy mice with otherwise normally developed mammary glands, characterized by greatly reduced milk protein synthesis coupled with epithelial cell death, inhibition of proliferation and a robust interferon response. Expression of mutant but not wild type Oas2 in cultured HC-11 or T47D mammary cells recapitulated the phenotypic and transcriptional effects observed in the mouse. The mutation activates the OAS2 pathway, demonstrated by a 34-fold increase in RNase L activity, and its effects were dependent on expression of RNase L and IRF7, proximal and distal pathway members. This is the first report of a viral recognition pathway regulating lactation. |
Keywords: | Mammary Glands, Animal Milk Animals Humans Mice Endoribonucleases 2',5'-Oligoadenylate Synthetase RNA, Double-Stranded Oligoribonucleotides Adenine Nucleotides Cell Culture Techniques Signal Transduction Lactation Mutation Female |
Rights: | © 2017 Oakes 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. |
DOI: | 10.1371/journal.pgen.1007072 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1047149 http://purl.org/au-research/grants/nhmrc/1058356 http://purl.org/au-research/grants/nhmrc/481310 http://purl.org/au-research/grants/nhmrc/1043400 http://purl.org/au-research/grants/arc/DP110102288 |
Published version: | http://dx.doi.org/10.1371/journal.pgen.1007072 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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hdl_120801.pdf | Published version | 8.3 MB | Adobe PDF | View/Open |
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