Mice deficient in oocyte-specific oligoadenylate synthetase-like protein OAS1D display reduced fertility

Mol Cell Biol. 2005 Jun;25(11):4615-24. doi: 10.1128/MCB.25.11.4615-4624.2005.


The double-stranded RNA (dsRNA)-induced interferon response is a defense mechanism against viral infection. Upon interferon activation by dsRNA, 2',5'-oligoadenylate synthetase 1 (OAS1A) is induced; it binds dsRNA and converts ATP into 2',5'-linked oligomers of adenosine (called 2-5A), which activate RNase L that in turn degrades viral and cellular RNAs. In a screen to identify oocyte-specific genes, we identified a novel murine cDNA encoding an ovary-specific 2',5'-oligoadenylate synthetase-like protein, OAS1D, which displays 59% identity with OAS1A. OAS1D is predominantly cytoplasmic and is exclusively expressed in growing oocytes and early embryos. Like OAS1A, OAS1D binds the dsRNA mimetic poly(I-C), but unlike OAS1A, it lacks 2'-5' adenosine linking activity. OAS1D interacts with OAS1A and inhibits the enzymatic activity of OAS1A. Mutant mice lacking OAS1D (Oas1d(-/-)) display reduced fertility due to defects in ovarian follicle development, decreased efficiency of ovulation, and eggs that are fertilized arrest at the one-cell stage. These effects are exacerbated after activation of the interferon/OAS1A/RNase L pathway by poly(I-C). We propose that OAS1D suppresses the interferon/OAS/RNase L-mediated cellular destruction by interacting with OAS1A during oogenesis and early embryonic development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / analysis
  • 2',5'-Oligoadenylate Synthetase / antagonists & inhibitors
  • 2',5'-Oligoadenylate Synthetase / genetics
  • 2',5'-Oligoadenylate Synthetase / metabolism
  • 2',5'-Oligoadenylate Synthetase / physiology*
  • Animals
  • Cytoplasm / chemistry
  • Cytoplasm / enzymology
  • Embryonic Development*
  • Female
  • Gene Expression
  • Infertility, Female / enzymology*
  • Interferon Inducers / pharmacology
  • Interferons / physiology
  • Male
  • Mice
  • Mice, Knockout
  • Oocytes / chemistry
  • Oocytes / cytology
  • Oocytes / enzymology*
  • Ovulation*
  • Poly I-C / pharmacology
  • Protein Biosynthesis
  • RNA, Double-Stranded / metabolism


  • Interferon Inducers
  • RNA, Double-Stranded
  • Interferons
  • Oas1d protein, mouse
  • 2',5'-Oligoadenylate Synthetase
  • Poly I-C