Disease relevance of Ifngr1

• Mice with a targeted disruption of the interferon gamma receptor gene (IFN-gamma R0/0 mice) and control wild-type mice were inoculated with the Bacillus Calmette-Guérin (BCG) strain of Mycobacterium bovis [1].
• Interferon gamma receptor deficient mice are resistant to endotoxic shock [2].
• LPS-induced lymphopenia, thrombocytopenia, and weight loss seen in wild-type mice were attenuated in IFN gamma R-/- mice [2].
• We report that IFN gamma R-/- mice have an increased resistance to LPS-induced toxicity, this resistance manifesting well before the synthesis and release of LPS-induced IFN-gamma [2].
• In contrast to genetically resistant 129Sv wildtype mice, IL-4/IFN-gamma R1 double mutant mice developed fetal disease with parasite dissemination to visceral organs similar to mice lacking IFN-gamma R1 only [3].

Psychiatry related information on Ifngr1

• The relatively increased resistance of IFN-gamma R(-/-) mice was not related to favorable effects on defense mechanisms known to contribute to antibacterial immunity-that is, the neutrophilic influx was reduced and the cytokine and nitric oxide levels were similar or lower in IFN-gamma R(-/-) mice [4].

High impact information on Ifngr1

• A cDNA clone was obtained that, upon stable transfection, rendered human HEp-2 cells expressing the murine IFN-gamma R fully responsive to murine IFN-gamma [5].
• Gene targeting in normal somatic cells: inactivation of the interferon-gamma receptor in myoblasts [6].
• The IFN-gamma-inducible signal transducing factor (STF-IFN gamma) was activated in murine TH2 but not in TH1 cell clones, because in the latter the second chain of the IFN-gamma receptor (accessory factor 1 or IFN-gamma R beta) was absent [7].
• Immune response in mice that lack the interferon-gamma receptor [8].
• Inhibition of methylcholanthrene-induced carcinogenesis by an interferon gamma receptor-dependent foreign body reaction [9].

Biological context of Ifngr1

• Thus, depressed TNF synthesis, diminished expression of CD14, and low plasma LPS-binding capacity, in addition to blocked IFN-gamma signaling in the mutant mice, likely to combine to manifest in the resistant phenotype of IFN gamma R-/- mice to endotoxin [2].
• As mouse Chromosome 10 carries the gene which encodes the interferon gamma-receptor (Ifgr), we used somatic cell hybrids that lack this chromosome [10].
• Interferon gamma receptors (IFN-gamma R) exhibit remarkable species specificity [11].
• In pregnant uteri, the highest proportions of IFN-gamma R mRNA were observed at gestation day (g.d.) 16 [12].
• In cycling uteri, the abundance of IFN-gamma R mRNA relative to an invariant message (glyceraldehyde-3-phosphate dehydrogenase) increased during progression of the hormonally regulated estrous cycle [12].

Anatomical context of Ifngr1

• Bone marrow and splenic macrophages from IFN gamma R-/- mice had a four- to sixfold decreased LPS-binding capacity which correlated with similar reduction in CD14 [2].
• The regulatory role of interferon-gamma receptor (IFN-gammaR)- and tumor necrosis factor receptor (TNFR)-mediated immune reactions for the activation of cerebral endothelial cells, microglia, and astrocytes was evaluated in a model of murine Toxoplasma encephalitis (TE) [13].
• IFN-gamma R mRNA in situ hybridization signals were slightly higher in macrophage-like than in other types of endometrial stromal cells [12].
• In contrast, activation of T cells, recruitment of immune cells to inflammatory foci, and anti-T. gondii IgM antibody production were unaffected by the mutation of the IFN-gamma R [14].
• In contrast the IFN-gamma R-/- mice showed a massive and generalized leucocytic infiltration of the airways and interstitium in which eosinophils were a prominent feature [15].

Associations of Ifngr1 with chemical compounds

• IFN gamma R-/- mice tolerated 100-1,000 times more LPS than the minimum lethal dose for wild-type mice in a D-galactosamine (D-GalN)/LPS model [2].
• Mice that lack the interferon-gamma receptor have profoundly altered responses to infection with Bacillus Calmette-Guérin and subsequent challenge with lipopolysaccharide [1].
• Oral feeding with KLH followed by parenteral immunization resulted in strongly suppressed SFC numbers and reduced cell-mediated immunity in both wild-type and IFN-gamma R -/- mice [16].
• Role of tyrosine 441 of interferon-gamma receptor subunit 1 in SOCS-1-mediated attenuation of STAT1 activation [17].
• Increased susceptibility of IFN-gamma R alpha o/o mice was associated with impaired nitric oxide (NO) production, as indicated by significantly lower plasma nitrite levels and by more transient expression of spleen inducible NO synthase mRNA [18].

Physical interactions of Ifngr1

• Transfected cells expressing both IFN-gamma R chains bind IFN-gamma with higher affinity than do cells expressing alpha chain alone [19].
• The hapten-induced upregulation of intercellular-adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) class I in IFN gamma-R-/- mice was smaller when compared to wild-type mice [20].
• Generation of nitric oxide and induction of major histocompatibility complex class II antigen in macrophages from mice lacking the interferon gamma receptor [21].

Co-localisations of Ifngr1

• As viewed by confocal microscopy, the immunopositivity for the IFN-gamma R was co-localized with that of the presynaptic marker synaptophysin and with neuronal nitric oxide synthase in the lateral spinal nucleus, whereas only a minor overlap with these molecules was observed in laminae I and II of the dorsal horn [22].

Regulatory relationships of Ifngr1

• Supernates that contained the secreted protein blocked binding of IFN-gamma to mouse IFN-gamma R and inhibited in a dose-dependent manner the IFN-gamma-mediated priming of mouse bone marrow culture-derived macrophages for tumor cell killing [23].

Other interactions of Ifngr1

• The level of IFNGR-1 mRNA also decreased in TLR2-stimulated RAW264.7 cells and M. avium-infected cells [24].
• In the present study, we show that TLR2 stimulation of RAW264.7 macrophages with a synthetic lipoprotein, Pam3CSK4, also causes rapid decrease in expression of IFNGR-1 protein, with little change in IFNGR-2 protein levels [24].
• The dramatically enhanced susceptibility of RAG-1-deficient, IFN-gamma R gene-deficient mice indicated the overall importance of innate immune cells in the release of protective levels of IFN-gamma [25].
• Effect of lack of Interleukin-4, Interleukin-12, Interleukin-18, or the Interferon-gamma receptor on virus replication, cytokine response, and lung pathology during respiratory syncytial virus infection in mice [26].
• The most likely gene order places the mutation between D10Mit80 and D10Mit16, near the interferon gamma receptor locus, Ifgr, which may be a candidate gene for this mutation [27].

Analytical, diagnostic and therapeutic context of Ifngr1

• Sequence analysis of the cDNA encoding the Mu-IFN-gamma R and comparison with the corresponding human IFN-gamma R sequence shows about 68% conservation of the extracellular domains and 51% conservation of the cytoplasmic domains at the nucleotide level [11].
• Despite potentially strong modulating effects of IFN-gamma on epithelial cell IgA transcytosis and electrolyte barrier functions, CT-immunized IFN-gamma R -/- mice demonstrated unaltered protection against CT in ligated intestinal loops together with normal anti-CT IgA and total IgA levels in gut lavage [16].
• We show that i.m. injections of this vector as naked DNA in mice results in secretion of IFN gamma R/IgG1, with serum levels exceeding 100 ng/ml for months after treatment [28].
• Prevention of autoimmune diabetes by intramuscular gene therapy with a nonviral vector encoding an interferon-gamma receptor/IgG1 fusion protein [28].
• Functional characterization of a hybrid human-mouse interferon gamma receptor: evidence for species-specific interaction of the extracellular receptor domain with a putative signal transducer [29].

References