Analysis Tools
mortality/aging
| N |
• homozygotes are viable, fertile and developmentally normal relative to wild-type mice
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immune system
| N |
• homozygotes show normal distribution of T cell subpopulations and % of activated T cells relative to wild-type mice
• homozygotes do not exhibit enhanced mortality upon exposure to mouse hepatitis virus under non-pathogen-free conditions
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• uninfected homozygotes show a significant decrease in total IgA fecal content; similarly, intragastrically-infected homozygotes exhibit significantly lower Candida-specific fecal IgA levels relative to wild-type mice
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• uninfected homozygotes display normal IgE production; however, after i.v. infection with C. albicans (PCA-2), homozygotes show reduced Candida-specific IgE levels relative to wild-type mice
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• uninfected homozygotes display normal IgG2a production; however, after i.v. infection with C. albicans (PCA-2), homozygotes show increased Candida-specific IgG2a levels relative to wild-type mice
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• in response to systemic challenge with a live vaccine strain of C. albicans, homozygotes fail to mount Th1-associated protective immunity and develop a T cell reactivity biased towards the Th2 pathway
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• in response to a low virulence C. albicans strain that normally induces Th1-mediated immunity in wild-type mice, infected homozygotes default to a Th2 response which can be redirected to the Th1 phenotype by IL-10 neutralization
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• non-ovariectomized homozygotes show normal osteoclastogenesis and osteoclast bone-resorbing activity, as shown by normal osteoclast surface and normal number of osteoclast precursors (CFU-GM) in the bone marrow
• however, unlike ovariectomized wild-type mice, homozygotes fail to exhibit increased numbers of CFU-GM in the bone marrow following estrogen depletion
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• after systemic or intragastric infection with C. albicans, homozygotes exhibit a greater increase in circulating IL-10 levels relative to wild-type mice
• notably, IL-10 neutralization increases Th1-mediated resistance in homozygotes with systemic candidiasis
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• Candidai-infected homozygotes exhibit reduced serum IL-12 levels relative to infected wild-type mice
• in contrast, serum IL-4 levels remain unaffected during candidiasis
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• homozygotes show increased susceptibility to either systemic or intragastric infection with virulent C. albicans relative to wild-type mice
• systemically infected homozygotes display increased fungal loads in the liver, kidney and brain
• intragastrically infected homozygotes show increased fungal growth in the stomach and esophagus, and increased yeast dissemination in the kidney, but are able to clear the mucosal infection as efficiently as wild-type mice
• notably, C. albicans-infected homozygotes do not develop as severe renal pathology in the cortex as the otherwise resistant wild-type mice
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skeleton
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• non-ovariectomized homozygotes display significantly reduced cortical bone volume relative to wild-type mice
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• non-ovariectomized homozygotes exhibit normal trabecular bone structure and volume relative to wild-type mice
• however, unlike ovariectomized wild-type mice, homozygotes fail to exhibit a 50% loss in trabecular bone volume following estrogen depletion
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• non-ovariectomized female homozygotes exhibit higher rates of bone turnover, despite normal trabecular volume
• unlike ovariectomized wild-type mice, homozygotes fail to exhibit a 50% bone loss or a 3- to 5-fold increase in indices of bone turnover and bone resorption following estrogen depletion
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• non-ovariectomized homozygotes show normal osteoclastogenesis and osteoclast bone-resorbing activity, as shown by normal osteoclast surface and normal number of osteoclast precursors (CFU-GM) in the bone marrow
• however, unlike ovariectomized wild-type mice, homozygotes fail to exhibit increased numbers of CFU-GM in the bone marrow following estrogen depletion
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homeostasis/metabolism
| N |
• homozygotes exhibit normal circadian variations in body temperature relative to wild-type mice
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• after systemic or intragastric infection with C. albicans, homozygotes exhibit a greater increase in circulating IL-10 levels relative to wild-type mice
• notably, IL-10 neutralization increases Th1-mediated resistance in homozygotes with systemic candidiasis
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• Candidai-infected homozygotes exhibit reduced serum IL-12 levels relative to infected wild-type mice
• in contrast, serum IL-4 levels remain unaffected during candidiasis
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• homozygotes fail to exhibit a febrile response to LPS (50 g/kg i.p) or recombinant murine (rm) IL-1beta (10 g/kg i.p or higher)
• homozygotes exhibit a small, atypical slow-onset fever response to a combination of i.p. injection of LPS plus recombinant human (rh) IL-6
• importantly, homozygotes display a rapid and long-lasting fever response to injection of rhIL-6 (500 ng/mouse i.c.v), but fail to exhibit a febrile response to rmIL-1beta (100 ng/mouse i.c.v)
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• male homozygotes exhibit reduced levels of dopamine in the hypothalamus
• striatal levels of HVA, the major metabolite of dopamine, are increased, suggesting a higher turnover for this neurotransmitter in the mutant striatum
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behavior/neurological
| N |
• 4-month-old homozygous males show a normal response to scopolamine-induced hypermotility relative to age-matched wild-type males
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• relative to wild-type males, mutant males exhibit a faster development of tolerance to the analgesic effect of morphine, indicating a modified opioid system
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• young and adult male homozygotes exhibit increased cognitive performance associated with a significant reduction in hippocampal choline acetyltransferase activity
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• under basal conditions, 4-month-old homozygous males show no increase in the step-through latency relative to wild-type males
• however, 4-month-old male homozygotes show a decreased response to scopolamine-induced amnesia
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• in the radial maze task, both young and adult male homozygotes display a better and faster acquisition, in terms of a reduced number of errors and days to reach the criterion, relative to age-matched wild-type males
• notably, 12 month-old homozygotes exhibit a faster acquisition (22 days vs 30 days to reach the criterion), with a robust tendency to enter an adjacent arm that is apparently lost in age-matched wild-type mice
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• male homozygotes display increased intermale aggression, already evident on the first encounter; by the 5th encounter, ~80% of mutant males become dominant whereas wild-type males divide themselves equally in dominants and subordinates (~50%)
• specifically, male homozygotes show a shorter latency to the first attack, an increased number of attacks, more chasing, less freezing, and a higher number and longer duration of offensive postures
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• male homozygotes fail to exhibit an analgesic response to a physical restraint stress
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• male homozygotes show no significant differences in the magnitude of basal nociceptive responses to a thermal stimulus
• however, male homozygotes exhibit a reduced analgesic response to the administration of low (1.25 mg/kg) but not high (2.5 mg/kg) doses of morphine
• in accord with a reduced opioid response, male homozygotes show a relevant reduction of mu opioid receptors in the midbrain, but not in the hypothalamus
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• male homozygotes tend to show reduced levels of affiliative behaviors, as shown by decreased rates of anogenital, nose or body sniffing relative to wild-type males
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hematopoietic system
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• uninfected homozygotes show a significant decrease in total IgA fecal content; similarly, intragastrically-infected homozygotes exhibit significantly lower Candida-specific fecal IgA levels relative to wild-type mice
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• uninfected homozygotes display normal IgE production; however, after i.v. infection with C. albicans (PCA-2), homozygotes show reduced Candida-specific IgE levels relative to wild-type mice
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• uninfected homozygotes display normal IgG2a production; however, after i.v. infection with C. albicans (PCA-2), homozygotes show increased Candida-specific IgG2a levels relative to wild-type mice
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• in response to systemic challenge with a live vaccine strain of C. albicans, homozygotes fail to mount Th1-associated protective immunity and develop a T cell reactivity biased towards the Th2 pathway
|
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• in response to a low virulence C. albicans strain that normally induces Th1-mediated immunity in wild-type mice, infected homozygotes default to a Th2 response which can be redirected to the Th1 phenotype by IL-10 neutralization
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• non-ovariectomized homozygotes show normal osteoclastogenesis and osteoclast bone-resorbing activity, as shown by normal osteoclast surface and normal number of osteoclast precursors (CFU-GM) in the bone marrow
• however, unlike ovariectomized wild-type mice, homozygotes fail to exhibit increased numbers of CFU-GM in the bone marrow following estrogen depletion
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