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Norway

PMID:29117179  

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

Samantha R Oakes | David Gallego-Ortega | Prudence M Stanford | Simon Junankar | Wendy Wing Yee Au | Zoya Kikhtyak | Anita von Korff | Claudio M Sergio | Andrew M K Law | Lesley E Castillo | Stephanie L Allerdice | Adelaide I J Young | Catherine Piggin | Belinda Whittle | Edward Bertram | Matthew J Naylor | Daniel L Roden | Jesse Donovan | Alexei Korennykh | Christopher C Goodnow | Moira K O'Bryan | Christopher J Ormandy
PLoS genetics | 2017

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.

Pubmed ID: 29117179

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM110161

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