Abstract
The interferon‐γ (IFN‐γ) receptor is expressed by all nucleated cells, and binding of its cognate ligand, IFN‐γ, induces a wide variety of biological functions. Transgenic mice expressing a dominant negative IFN‐γ receptor 1 (IFN‐γR1ΔIC) on oligodendrocytes under control of the myelin proteolipid protein promoter are described. The mRNA encoding the transgene was only detected in the nervous system and protein expression was confirmed by immunohistochemistry. Transgenic receptor expression does not alter myelination and the mice exhibited no clinically apparent phenotype. Consistent with the restricted nervous system expression of the transgene, no alterations in peripheral immune responses were detected. Flow cytometric analysis demonstrated constitutive expression of both the IFN‐γR1ΔIC transgene and the endogenous IFN‐γ receptor 2 at high levels on oligodendrocytes derived from the transgenic mice. These oligodendrocytes also exhibited decreased STAT1 phosphorylation in response to IFN‐γ, confirming dominant negative transgene function. Transgenic mice in which oligodendrocytes have a diminished ability to respond to IFN‐γ showed delayed virus clearance from oligodendroglia compared with wild‐type mice. This model will allow evaluation of oligodendrocyte responses to this critical cytokine during CNS inflammation.© 2005 Wiley‐Liss, Inc.