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

Author(s): Oakes, Samantha R.; Gallego-Ortega, David; Stanford, Prudence M.; Junankar, Simon; Au, Wendy Wing Yee; et al

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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.
Publication Date: 8-Nov-2017
Citation: Oakes, Samantha R, Gallego-Ortega, David, Stanford, Prudence M, Junankar, Simon, Au, Wendy Wing Yee, Kikhtyak, Zoya, von Korff, Anita, Sergio, Claudio M, Law, Andrew MK, Castillo, Lesley E, Allerdice, Stephanie L, Young, Adelaide IJ, Piggin, Catherine, Whittle, Belinda, Bertram, Edward, Naylor, Matthew J, Roden, Daniel L, Donovan, Jesse, Korennykh, Alexei, Goodnow, Christopher C, O'Bryan, Moira K, Ormandy, Christopher J. (2017). A mutation in the viral sensor 2'-5'-oligoadenylate synthetase 2 causes failure of lactation. PLoS Genetics, 13 (11), e1007072 (1 - 24). doi:10.1371/journal.pgen.1007072
DOI: doi:10.1371/journal.pgen.1007072
ISSN: 1553-7390
EISSN: 1553-7404
Pages: e1007072 (1 - 24)
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: PLoS Genetics
Version: Final published version. This is an open access article.

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