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

Oakes, SR; Gallego-Ortega, D; Stanford, PM; Junankar, S; Au, WWY; Kikhtyak, Z; von Korff, A; Sergio, CM; Law, AMK; Castillo, LE; Allerdice, SL; Young, AIJ; Piggin, C; Whittle, B; Bertram, E; Naylor, MJ; Roden, DL; Donovan, J; Korennykh, A; Goodnow, CC; O'Bryan, MK; Ormandy, CJ

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

Oakes, SR Gallego-Ortega, D Stanford, PM Junankar, S Au, WWY Kikhtyak, Z von Korff, A Sergio, CM Law, AMK Castillo, LE Allerdice, SL Young, AIJ Piggin, C Whittle, B Bertram, E Naylor, MJ Roden, DL Donovan, J Korennykh, A Goodnow, CC O'Bryan, MK Ormandy, CJ

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Publisher:: PUBLIC LIBRARY SCIENCE
Publication Type:: Journal Article
Citation:: PLoS Genet, 2017, 13, (11), pp. e1007072
Issue Date:: 2017-11

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Field	Value	Language
dc.contributor.author	Oakes, SR
dc.contributor.author	Gallego-Ortega, D
dc.contributor.author	Stanford, PM
dc.contributor.author	Junankar, S
dc.contributor.author	Au, WWY
dc.contributor.author	Kikhtyak, Z
dc.contributor.author	von Korff, A
dc.contributor.author	Sergio, CM
dc.contributor.author	Law, AMK
dc.contributor.author	Castillo, LE
dc.contributor.author	Allerdice, SL
dc.contributor.author	Young, AIJ
dc.contributor.author	Piggin, C
dc.contributor.author	Whittle, B
dc.contributor.author	Bertram, E
dc.contributor.author	Naylor, MJ
dc.contributor.author	Roden, DL
dc.contributor.author	Donovan, J
dc.contributor.author	Korennykh, A
dc.contributor.author	Goodnow, CC
dc.contributor.author	O'Bryan, MK
dc.contributor.author	Ormandy, CJ
dc.date.accessioned	2022-04-13T12:25:19Z
dc.date.available	2017-10-11
dc.date.available	2022-04-13T12:25:19Z
dc.date.issued	2017-11
dc.identifier.citation	PLoS Genet, 2017, 13, (11), pp. e1007072
dc.identifier.issn	1553-7390
dc.identifier.issn	1553-7404
dc.identifier.uri	http://hdl.handle.net/10453/156217
dc.description.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.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	PUBLIC LIBRARY SCIENCE
dc.relation.ispartof	PLoS Genet
dc.relation.isbasedon	10.1371/journal.pgen.1007072
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0604 Genetics
dc.subject.classification	Developmental Biology
dc.subject.mesh	2',5'-Oligoadenylate Synthetase
dc.subject.mesh	Adenine Nucleotides
dc.subject.mesh	Animals
dc.subject.mesh	Cell Culture Techniques
dc.subject.mesh	Endoribonucleases
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	Lactation
dc.subject.mesh	Mammary Glands, Animal
dc.subject.mesh	Mice
dc.subject.mesh	Milk
dc.subject.mesh	Mutation
dc.subject.mesh	Oligoribonucleotides
dc.subject.mesh	RNA, Double-Stranded
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Mammary Glands, Animal
dc.subject.mesh	Milk
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Endoribonucleases
dc.subject.mesh	2',5'-Oligoadenylate Synthetase
dc.subject.mesh	RNA, Double-Stranded
dc.subject.mesh	Oligoribonucleotides
dc.subject.mesh	Adenine Nucleotides
dc.subject.mesh	Cell Culture Techniques
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Lactation
dc.subject.mesh	Mutation
dc.subject.mesh	Female
dc.title	A mutation in the viral sensor 2'-5'-oligoadenylate synthetase 2 causes failure of lactation.
dc.type	Journal Article
utslib.citation.volume	13
utslib.location.activity	United States
utslib.for	0604 Genetics
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2022-04-13T12:25:11Z
pubs.issue	11
pubs.publication-status	Published online
pubs.volume	13
utslib.citation.issue	11

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.

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http://hdl.handle.net/10453/156217