Production of Immunoreactive 2′,5′-Oligoadenylate Synthetase in p48-Deficient Mice

Abstract

2′,5′-Oligoadenylate synthetase (2′5′OAS), an enzyme induced by interferon (IFN), is physiologically produced in IFN-untreated normal healthy mice. The enzyme is localized mainly in the epithelium of the digestive tract, reproductive organs, and the choroid plexus in the brain. 2′5′OAS is also detected in oocytes in the ovary and in neurons and glial cells of both the telencephalon and cerebellum. Here, we examined the role of p48 (ISGF3γ), a component of IFN-stimulated gene factor 3 (ISGF3), in the physiologic production of 2′5′OAS using p48-deficient mice generated by gene targeting. In the p48-deficient mice, the physiologic production of 2′5′OAS localized in the following cells was severely impaired: hepatocytes, Kupffer cells, splenocytes, epithelium of the large intestine, oviduct, and uterus, and neurons and glial cells in both the telencephalon and cerebellum. The results show that 2′5′OAS in these cells is induced physiologically through a pathway including p48. However, the production of 2′5′OAS in oocytes was not affected in the p48-deficient mice, indicating that oocyte 2′5′OAS is produced through a p48-independent pathway. A possible function of the GAS sequence found in the promoter region of the 2′5′OAS gene to which Stat6 may bind also is discussed.