mortality/aging
N |
• homozygotes are viable, fertile and developmentally normal; no significant differences in body weight, core body temperature, or hematology are observed
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behavior/neurological
• at 3 months, homoygotes exhibit normal brain neurochemistry with respect to total monoamine content, as well as normal spatial learning (Morris water maze task), locomotor activity (open-field), motor function (rotarod), and anxiety-like behavior (light/dark exploration test)
• however, homozygotes exhibit a selective increase in Pavlovian conditioned fear, with markedly increased freezing levels after long (i.e 24-hr) retention intervals; no significant differences are noted during the 30-min context test
• notably, homozygotes do not exhibit enhanced auditory-cue-conditioned fear, and serotonin and norepinephrine levels remain normal in mutant cortex
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homeostasis/metabolism
• TNF-alpha, IL-6, and MIP-2 levels are decreased by 85%, 60% and 45%, respectively, in mutants compared to wild-type mice following intratracheal instillation of LPS
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• mutants exhibit reduced lung injury following intratracheal instillation of lipopolysaccharide (LPS), showing decreased neutrophil accumulation, negligible intra-alveolar hemorrhage, diminished albumin levels in bronchial alveolar lavage (BAL) fluids, decrease in MPO activity, fewer neutrophils but increased macrophages in BAL fluids, and decreased TNF-alpha, IL-6 and MIP-2 levels compared to similarly treated wild-type mice
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immune system
• TNF-alpha, IL-6, and MIP-2 levels are decreased by 85%, 60% and 45%, respectively, in mutants compared to wild-type mice following intratracheal instillation of LPS
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• mutants exhibit reduced inflammatory cell influx into the lungs following intratracheal instillation of LPS to induce lung damage compared to wild-type mice, showing attenuation of neutrophil accumulation
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respiratory system
• mutants exhibit reduced lung injury following intratracheal instillation of LPS, showing decreased neutrophil accumulation, negligible intra-alveolar hemorrhage, diminished albumin levels in BAL fluids, decrease in MPO activity, fewer neutrophils but increased macrophages in BAL fluids, and decreased TNF-alpha, IL-6 and MIP-2 levels compared to similarly treated wild-type mice
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