| First Author | Oakes SR | Year | 2017 |
| Journal | PLoS Genet | Volume | 13 |
| Issue | 11 | Pages | e1007072 |
| PubMed ID | 29117179 | Mgi Jnum | J:248944 |
| Mgi Id | MGI:6094812 | Doi | 10.1371/journal.pgen.1007072 |
| Citation | Oakes SR, et al. (2017) A mutation in the viral sensor 2'-5'-oligoadenylate synthetase 2 causes failure of lactation. PLoS Genet 13(11):e1007072 |
| abstractText | 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. |
