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A mutation in the viral sensor 2’-5’-oligoadenylate synthetase 2 causes failure of lactation.
- Source :
- PLoS Genetics; 11/08/2017, Vol. 13 Issue 11, p1-24, 24p
- Publication Year :
- 2017
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15537390
- Volume :
- 13
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- PLoS Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 126108738
- Full Text :
- https://doi.org/10.1371/journal.pgen.1007072