Premium
Astrocyte expression of a dominant‐negative interferon‐γ receptor
Author(s) -
Hindinger Claudia,
Gonzalez John M.,
Bergmann Cornelia C.,
Fuss Babette,
Hinton David R.,
Atkinson Roscoe D.,
Macklin Wendy B.,
Stohlman Stephen A.
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20616
Subject(s) - astrocyte , biology , glial fibrillary acidic protein , transgene , genetically modified mouse , receptor , immunology , proinflammatory cytokine , interferon , microbiology and biotechnology , inflammation , central nervous system , endocrinology , immunohistochemistry , gene , biochemistry
Interferon‐γ (IFN‐γ) is a major proinflammatory cytokine, and binding to its nearly ubiquitous receptor induces a wide variety of biological functions. To explore the role(s) of IFN‐γ signaling in astrocytes, transgenic mice (GFAP/IFN‐γR1ΔIC) expressing a dominant‐negative IFN‐γ receptor alpha chain under control of the astrocyte‐specific glial fibrillary acid protein (GFAP) promoter were generated. Transgenic mice developed normally, had normal astrocyte numbers and distribution, and exhibited no clinically overt phenotype. Transgene mRNA expression was detected only in the CNS, and the transgene‐encoded IFN‐γ receptor 1 colocalized with GFAP, which is consistent with astrocyte expression. Astrocytes from transgenic mice exhibited reduced IFN‐γ‐induced signaling as measured by major histocompatibility class II induction. Neither CNS inflammation nor perforin‐mediated clearance of a neurotropic mouse hepatitis virus from astrocytes was impaired following infection. Transgenic mice with impaired astrocyte responsiveness to IFN‐γ provide a model for studying the selective astrocyte‐dependent effects of this critical cytokine in CNS immunopathology. © 2005 Wiley‐Liss, Inc.