Analysis Tools
hearing/vestibular/ear
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• at P23, no ABR thresholds are detected in response to 85 dB SPL
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Allele Symbol Allele Name Allele ID |
Tmtc4tm1(KOMP)Vlcg targeted mutation 1, Velocigene MGI:5008116 |
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| Summary |
3 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at P23, no ABR thresholds are detected in response to 85 dB SPL
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• immunohistochemistry of cochlear explants revealed progressive loss of first outer hair cell (OHCs) and then inner hair cells (IHCs) at the cochlear base and subsequently at the mid-turn and apex
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• by P26, mice show degeneration of the supporting cell network in the organ of Corti
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• mice show generalized and progressive cochlear degeneration affecting first hair cells, and subsequently the supporting cell network and spiral ganglion neurons
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• at P30, degeneration of the organ of Corti is observed in all cochlear turns
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• at P26, ABR waveforms indicate absent ABR responses to click stimuli at multiple sound pressure levels (SPL)
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• at P26, mice show significantly increased ABR thresholds in response to both broadband click and a range of pure-tone frequencies relative to wild-type or heterozygous control mice
• however, ABR thresholds to broadband click stimuli are normal at P13
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• DPOAEs are absent at P26
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• mice exhibit early onset, rapidly progressive hearing loss and become nearly completely deaf by P23
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• immunohistochemistry of cochlear explants revealed progressive loss of first outer hair cell (OHCs) and then inner hair cells (IHCs) at the cochlear base and subsequently at the mid-turn and apex
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• at 4 months of age, mice show degeneration of the spiral ganglion neurons
• however, the spiral ganglion is preserved at P30
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• thapsigargin-treated neonatal skin fibroblasts show significantly higher protein levels of Chop as well as the downstream UPR protein DR5, and the apoptosis marker cleaved caspase 8 relative to similarly-treated wild-type fibroblasts
• thapsigargin-treated neonatal cochlear explant cultures show elevated caspase 3 mRNA levels (indicating apoptosis) relative to similarly-treated wild-type cultures
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• cochleae exhibit significantly increased spontaneous Ca2+ wave frequency, higher [Ca2+]i peak levels, and significantly longer decay time of [Ca2+] return to baseline, suggesting impaired Ca2+ reuptake into the endoplasmic reticulum
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• thapsigargin-treated neonatal skin fibroblasts exhibit upregulation of the unfolded protein response (UPR), as shown by significantly higher mRNA levels of 3 genes (Chop, S-XBP1, and BiP) relative to similarly-treated wild-type fibroblasts
• steady-state Chop protein levels are markedly higher than those in wild-type fibroblasts, with 29.9% of cells versus 0.5% of wild-type cells showing expression levels above threshold, even in the absence of thapsigargin
• thapsigargin-treated neonatal cochlear explant cultures show significantly higher mRNA levels of UPR activators (Chop, S-XBP1, and BiP) as well as elevated caspase 3 mRNA levels (indicating apoptosis) relative to similarly-treated wild-type cultures
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• cochleae exhibit significantly increased spontaneous Ca2+ wave frequency, higher [Ca2+]i peak levels, and significantly longer decay time of [Ca2+] return to baseline, suggesting impaired Ca2+ reuptake into the endoplasmic reticulum
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at P19, double homozygotes exhibit improved ABR thresholds relative to single Tmtc4tm1(KOMP)Vlcg homozygotes
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• double homozygotes exhibit less severe hearing loss than single Tmtc4tm1(KOMP)Vlcg homozygotes
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/16/2024 MGI 6.23 |
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