Analysis Tools
hearing/vestibular/ear
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• at 1 and 3 months, vacuole-like spaces replace the afferent terminals of the inner radial nerves while efferent inner spiral fibers appear intact
• at 1 and 3 months, edematous-appearing extracellular spaces are noted between the IHC and supporting cells; the cytoplasm in the base of IHCs consists of numerous small vesicles infiltrated with mitochondria and short profiles of cisternae
• in contrast, no major pathological changes are seen in mutant OHCs or stria vascularis at 1 or 3 months
• all homozygotes (6 of 6) exhibit excitotoxic pathologies of afferent dendrites under the IHCs compared with 4 of 9 in wild-type mice
• homozygotes show a significantly higher number of swollen dendritic terminals per IHC region relative to wild-type mice; only type I ganglion neurons are involved
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• at 1 month of age, CAP thresholds in homozygotes are elevated by 6-20 dB SPL relative to wild-type mice at almost all frequencies
• at 3 months of age, mutant CAP thresholds are increased by ~20 dB SPL at low frequencies and by ~30 dB at high frequencies relative to wild-type
• by 8 months of age, most homozygotes no longer respond to auditory stimuli at high frequencies (90 dB SPL), whereas wild-type mice retain CAP responses at most test frequencies
• at 3 months, no sigificant loss of distorion product otoacoustic emissions (DPOAEs) is noted when primaries are presented at 70 dB SPL
• no significant differences in mean endocochlear potential values are observed at 1, 3, and 8 months of age relative to wild-type mice
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• homozygotes exhibit accelerated age-related hearing loss at higher frequencies, as assessed by CAP threshold shifts at 1, 3, and 8 months of age
• accelerated hearing loss is highly associated with an exacerbated excitotoxic-like damage in afferent dendrites under IHCs and an accelerated loss of spiral ganglion neurons
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• at 2 hrs after exposure to a wideband, low-level noise at 70 dB SPL, 1-month-old homozygotes display 7-15 dB SPL threshold shifts across most test frequencies whereas wild-type mice show no significant CAP threshold shifts
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nervous system
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• at 1 and 3 months, vacuole-like spaces replace the afferent terminals of the inner radial nerves while efferent inner spiral fibers appear intact
• at 1 and 3 months, edematous-appearing extracellular spaces are noted between the IHC and supporting cells; the cytoplasm in the base of IHCs consists of numerous small vesicles infiltrated with mitochondria and short profiles of cisternae
• in contrast, no major pathological changes are seen in mutant OHCs or stria vascularis at 1 or 3 months
• all homozygotes (6 of 6) exhibit excitotoxic pathologies of afferent dendrites under the IHCs compared with 4 of 9 in wild-type mice
• homozygotes show a significantly higher number of swollen dendritic terminals per IHC region relative to wild-type mice; only type I ganglion neurons are involved
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• at 1 month of age, CAP thresholds in homozygotes are elevated by 6-20 dB SPL relative to wild-type mice at almost all frequencies
• at 3 months of age, mutant CAP thresholds are increased by ~20 dB SPL at low frequencies and by ~30 dB at high frequencies relative to wild-type
• by 8 months of age, most homozygotes no longer respond to auditory stimuli at high frequencies (90 dB SPL), whereas wild-type mice retain CAP responses at most test frequencies
• at 3 months, no sigificant loss of distorion product otoacoustic emissions (DPOAEs) is noted when primaries are presented at 70 dB SPL
• no significant differences in mean endocochlear potential values are observed at 1, 3, and 8 months of age relative to wild-type mice
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• at 8 months, homozygotes show a 69% loss of SGNs in the basal cochlea relative to a ~28% loss observed in wild-type mice
• at 8 months, the numbers of afferent axons per habenular opening are significantly reduced relative to those of wild-type mice
• however, no significant differences in IHC or OHC loss are noted at 8 months relative to wild-type mice
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homeostasis/metabolism
| N |
• despite altered expression of Trp53, neurons exhibit normal camptothecin-induced neuronal death
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• at 8 months, the immunoreactivity for a set of calcium-buffering proteins is significantly increased in mutant spiral ganglion neurons, suggesting impaired calcium ion homeostasis
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immune system
| N |
• most pancreatic islet cells appear normal in mutants not developing diabetes after streptozotocin treatment, while control pancreatic islets display insulitis; mutants developing diabetes after treatment display insulis in many islets
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• splenocytes treated with anti-CD3 with or without anti-CD28 antibodies produce reduced levels of interferon gamma and Il-2 (Th1 cytokines) but increased levels of Il-4 and Il-10 (Th2 cytokines) while wild-type splenocytes produce both Th1 and Th2 cytokines
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• peritoneal macrophages produce less Il-6, Il-12p40, TNF alpha, and nitric oxide compared to wild-type cells upon stimulation with interferon gamma and/or LPS
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• bone marrow-derived dendritic cells stimulated with LPS produce significantly less Il-12p40 and TNF alpha than stimulated wild-type dendritic cells
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• Il-4 secretion is impaired in cultured cells upon stimulation with MOG peptide
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• >70% of control mice treated with low dose streptozotocin for 5 days develop diabetes starting ~8 and 12 days after the first injection, but only 23% of mutants develop diabetes
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cellular
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• growth factor withdrawal from cultured bone marrow dendritic cells enhances apoptosis of dendritic cells, but not granulocytes or macrophages
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muscle
| N |
• myogenesis is normal
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hematopoietic system
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• splenocytes treated with anti-CD3 with or without anti-CD28 antibodies produce reduced levels of interferon gamma and Il-2 (Th1 cytokines) but increased levels of Il-4 and Il-10 (Th2 cytokines) while wild-type splenocytes produce both Th1 and Th2 cytokines
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• peritoneal macrophages produce less Il-6, Il-12p40, TNF alpha, and nitric oxide compared to wild-type cells upon stimulation with interferon gamma and/or LPS
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