A mutation in the viral sensor 2'-5'-oligoadenylate synthetase 2 causes failure of lactation.
PLoS Genet
; 13(11): e1007072, 2017 Nov.
Article
em En
| MEDLINE
| ID: mdl-29117179
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
2',5'-Oligoadenilato Sintetase
/
Lactação
Tipo de estudo:
Etiology_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
PLoS Genet
Assunto da revista:
GENETICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Austrália