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

作者：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 M K; Castillo Lesley E; Allerdice Stephanie L; Young Adelaide I J; 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

来源：PLoS Genetics, 2017, 13(11): e1007072.

DOI：10.1371/journal.pgen.1007072

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.

• 出版日期2017-11
• 单位河北医科大学