A mutation in the viral sensor 2’-5’-oligoadenylate synthetase 2 causes failure of lactation

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dc.contributor.authorOakes, S.R.
dc.contributor.authorGallego-Ortega, D.
dc.contributor.authorStanford, P.M.
dc.contributor.authorJunankar, S.
dc.contributor.authorAu, W.W.Y.
dc.contributor.authorKikhtyak, Z.
dc.contributor.authorvon Korff, A.
dc.contributor.authorSergio, C.M.
dc.contributor.authorLaw, A.M.K.
dc.contributor.authorCastillo, L.E.
dc.contributor.authorAllerdice, S.L.
dc.contributor.authorYoung, A.I.J.
dc.contributor.authorPiggin, C.
dc.contributor.authorWhittle, B.
dc.contributor.authorBertram, E.
dc.contributor.authorNaylor, M.J.
dc.contributor.authorRoden, D.L.
dc.contributor.authorDonovan, J.
dc.contributor.authorKorennykh, A.
dc.contributor.authorGoodnow, C.C.
dc.contributor.authoret al.
dc.contributor.editorWells, C.A.
dc.date.issued2017
dc.description.abstractWe 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.
dc.description.statementofresponsibilitySamantha R. Oakes, David Gallego-Ortega, Prudence M. Stanford, Simon Junankar, Wendy Wing Yee Au ... Moira K. O’Bryan ... et al.
dc.identifier.citationPLoS Genetics, 2017; 13(11):e1007072-1-e1007072-24
dc.identifier.doi10.1371/journal.pgen.1007072
dc.identifier.issn1553-7390
dc.identifier.issn1553-7404
dc.identifier.orcidKikhtyak, Z. [0000-0002-3472-6067]
dc.identifier.urihttp://hdl.handle.net/2440/120801
dc.language.isoen
dc.publisherPublic Library Science
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1047149
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1058356
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/481310
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1043400
dc.relation.granthttp://purl.org/au-research/grants/arc/DP110102288
dc.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.
dc.source.urihttps://doi.org/10.1371/journal.pgen.1007072
dc.subjectMammary Glands, Animal
dc.subjectMilk
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectEndoribonucleases
dc.subject2',5'-Oligoadenylate Synthetase
dc.subjectRNA, Double-Stranded
dc.subjectOligoribonucleotides
dc.subjectAdenine Nucleotides
dc.subjectCell Culture Techniques
dc.subjectSignal Transduction
dc.subjectLactation
dc.subjectMutation
dc.subjectFemale
dc.titleA mutation in the viral sensor 2’-5’-oligoadenylate synthetase 2 causes failure of lactation
dc.typeJournal article
pubs.publication-statusPublished

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