Analysis Tools
hearing/vestibular/ear
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• at E15.5, a small number of fresh postmitotic hair cells are abnormally retained in the supporting cell layer of vestibular sensory epithelia, indicating improper migration into the luminal cell layer
(J:43752)
• at P8, ~20% of immature hair cells are present in mutant vestibular sensory epithelia
(J:82156)
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• the apical surface of the organ of Corti lacks stereociliary bundles and is apparently composed of a contiguous sheet of supporting cells bearing microvilli
(J:42478)
• at P8, the spiral capillary is not located below the organ of Corti but in the spiral limbus nearby
(J:82156)
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• at P7/P8, pillar cells remain undifferentiated almost throughout the cochlea
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• at P8, only 1% of myosin VIIa-positive immature hair cells are present in the apical turn of the cochlea; not a single immature hair cell forms in the cochlear apex
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• the apical surface of the organ of Corti lacks stereociliary bundles
(J:42478)
• by P8, no mature stereociliary bundles are identified in the cochlear labyrinth; however, initial generation and differentiation of cochlear hair cells is normal
(J:43752)
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• at E18.5 or P0, very small IHCs with poor luminal surface differentiation are noted in the apical region while no IHCs can be detected at the base
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• at E18.5 or P0, IHCs of the apical cochlear region appear to lack stereocilia
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• at P0, both afferent and efferent fiber outgrowth to the outer hair cells is disorganized
(J:82156)
• at E18.5, OHC morphology and patterning is markedly abnormal, esp. in the basal region of the cochlea
(J:92833)
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• at E18.5, no intact OHC stereociliary bundles can be identified with phalloidin staining
• at E18.5 or P0, the luminal surface of OHCs throughout the length of the cochlea is composed of a sheath of poorly differentiated and disorganized apical projections and poorly defined cell boundaries
• at P0, long and aberrant stereocilia-like structures are identified on the surface of some degenerating OHCs
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• homozygotes exhibit progressive disorganization and loss of cochlear hair cells as early as E17.5, with nearly complete loss by P5
(J:42478)
• at E18.5 and early postnatal stages, hair cell numbers are severely reduced in the organ of Corti via apoptosis
(J:43752)
• at P0, most of the basal sensory epithelium has degenerated
(J:92833)
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• by P5, homozygotes lack identifiable IHCs in the organ of Corti
(J:42478)
• at E18.5, IHCs are readily identified in the apex but are clearly absent from the most basal 30-35% of the cochlear duct
(J:92833)
• less severe IHC degeneration is noted at E16.5
(J:92833)
• at P0, no IHCs can be identified in the basal parts
(J:92833)
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• by P5, homozygotes lack identifiable OHCs in the organ of Corti
(J:42478)
• no cholinergic innervation of OHCs is detected, as shown by absence of acetylcholine esterase activity
(J:42478)
• at E18.5, homozygotes exhibit OHC degeneration in the base and apex of the cochlea; less severe OHC degeneration is noted at E16.5
(J:92833)
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• Deiter's-like cells are variably present
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• at P7/P8, no Deiters' cells are recognizable based on morphology
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• adult homozygotes show absence of supporting cells
• typically, only a single cell type, presumably the cells of Hensen, are detected above the basilar membrane
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• pillar cells are absent or rudimentary
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• at E18.5, a slow degeneration of pillar cells occurs in a wave that begins from the base of the cochlea toward the apex
• at this stage, an undisrupted row of pillar cells is clearly present in the apex
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• by P8, no mature stereociliary bundles are identified in the vestibular labyrinth; however, initial generation and differentiation of vestibular hair cells is normal
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• homozygotes exhibit progressive disorganization and loss of vestibular hair cells as early as E17.5, with nearly complete loss by P5
(J:42478)
• by P5, homozygotes lack hair cells in the otolith organs; the sensory epithelium contains only supporting cells
(J:42478)
• at E18.5, homozygotes show only 27%, 28% and 26%, respectively, of hair cells in the sensory epithelia of the saccule, utricle and cristae
(J:43752)
• at P4, these numbers are reduced to ~23%, 15%, and 12%, respectively, via apoptosis (as shown by TUNEL labeling)
(J:43752)
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• by P5, homozygotes lack hair cells in the cristae; the sensory epithelium contains only supporting cells
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• unlike heterozygotes and wild-type mice which have an auditory threshold of ~50 dB SPL, homozygotes show no auditory brainstem responses at any stimulus level, including 114 dB SPL
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behavior/neurological
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• homozygotes fail to exhibit a robust startle response upon exposure to a sharp sound
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• homozygotes show an extremely poor balance, falling from a stationary drum within 10 sec; when the drum is slowly rotated, no animals remain on the drum after 5 sec
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• all homozygotes fail to remain upright and swim effectively in a tub of water
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nervous system
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• at P8, only 1% of myosin VIIa-positive immature hair cells are present in the apical turn of the cochlea; not a single immature hair cell forms in the cochlear apex
|
|
• at E15.5, a small number of fresh postmitotic hair cells are abnormally retained in the supporting cell layer of vestibular sensory epithelia, indicating improper migration into the luminal cell layer
(J:43752)
• at P8, ~20% of immature hair cells are present in mutant vestibular sensory epithelia
(J:82156)
|
|
• the apical surface of the organ of Corti lacks stereociliary bundles
(J:42478)
• by P8, no mature stereociliary bundles are identified in the cochlear labyrinth; however, initial generation and differentiation of cochlear hair cells is normal
(J:43752)
|
|
• at E18.5 or P0, very small IHCs with poor luminal surface differentiation are noted in the apical region while no IHCs can be detected at the base
|
|
• at E18.5 or P0, IHCs of the apical cochlear region appear to lack stereocilia
|
|
• at P0, both afferent and efferent fiber outgrowth to the outer hair cells is disorganized
(J:82156)
• at E18.5, OHC morphology and patterning is markedly abnormal, esp. in the basal region of the cochlea
(J:92833)
|
|
• at E18.5, no intact OHC stereociliary bundles can be identified with phalloidin staining
• at E18.5 or P0, the luminal surface of OHCs throughout the length of the cochlea is composed of a sheath of poorly differentiated and disorganized apical projections and poorly defined cell boundaries
• at P0, long and aberrant stereocilia-like structures are identified on the surface of some degenerating OHCs
|
|
• homozygotes exhibit progressive disorganization and loss of cochlear hair cells as early as E17.5, with nearly complete loss by P5
(J:42478)
• at E18.5 and early postnatal stages, hair cell numbers are severely reduced in the organ of Corti via apoptosis
(J:43752)
• at P0, most of the basal sensory epithelium has degenerated
(J:92833)
|
|
• by P5, homozygotes lack identifiable IHCs in the organ of Corti
(J:42478)
• at E18.5, IHCs are readily identified in the apex but are clearly absent from the most basal 30-35% of the cochlear duct
(J:92833)
• less severe IHC degeneration is noted at E16.5
(J:92833)
• at P0, no IHCs can be identified in the basal parts
(J:92833)
|
|
• by P5, homozygotes lack identifiable OHCs in the organ of Corti
(J:42478)
• no cholinergic innervation of OHCs is detected, as shown by absence of acetylcholine esterase activity
(J:42478)
• at E18.5, homozygotes exhibit OHC degeneration in the base and apex of the cochlea; less severe OHC degeneration is noted at E16.5
(J:92833)
|
|
• by P8, no mature stereociliary bundles are identified in the vestibular labyrinth; however, initial generation and differentiation of vestibular hair cells is normal
|
|
• homozygotes exhibit progressive disorganization and loss of vestibular hair cells as early as E17.5, with nearly complete loss by P5
(J:42478)
• by P5, homozygotes lack hair cells in the otolith organs; the sensory epithelium contains only supporting cells
(J:42478)
• at E18.5, homozygotes show only 27%, 28% and 26%, respectively, of hair cells in the sensory epithelia of the saccule, utricle and cristae
(J:43752)
• at P4, these numbers are reduced to ~23%, 15%, and 12%, respectively, via apoptosis (as shown by TUNEL labeling)
(J:43752)
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• at P0, homozygotes show only a reduced density of afferent and efferent fibers to all vestibular sensory epithelia, with no specific loss of all afferent and efferent innervation to the canal crista; no increase in radial fiber spacing is noted in the apex
• at P7/P8, innervation is severely reduced both qualitatively and quantitatively
• despite a more severe loss of hair cells (1% in cochlea vs 20% in vestibular epithelia), the cochlea retains many more sensory neurons than vestibular epithelia (46% vs 15%)
• at 6 months, homozygotes show long term retention of cochlear sensory neurons, esp. in the cochlear apex
• retention of afferents and efferents is unrelated to hair cell differentiation, as not even immature hair cells are detectable at early postnatal stages in the cochlear apex
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• adult homozygotes have cochlear ganglia with less than one-tenth as many myelinated axons and neuronal cell bodies relative to wild-type mice
(J:42478)
• neuronal loss is minimal at E17.5, with reduced numbers of neurons at P1 and P5, and severe depletion of neurons and myelinated fibers by several months of age
(J:42478)
• at E18.5, mutant spiral ganglia show a ~13% loss of neurons
(J:43752)
• at E18.5 and P0, homozygotes show a 83%-140% increase in the number of TUNEL+ apoptotic cells in the spiral ganglion
(J:43752)
• by P4, ~29% of neurons are lost and mutant spiral ganglia become overtly smaller than wild-type
(J:43752)
• at P7, 46% of spiral ganglion neurons are lost overall with a less severe loss in the apex
(J:82156)
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• at P0, homozygotes exhibit reduced vestibular ganglia, consistent with a 77% loss of vestibular ganglion neurons at P4
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• adult homozygotes exhibit few or no myelinated axons beneath the otolith organs
(J:42478)
• neuronal loss is minimal at E17.5, with reduced numbers of neurons at P1 and P5, and severe depletion of neurons and myelinated fibers by several months of age
(J:42478)
• in contrast, no differences in the size, number, or arrangement of neurons in the retina, dorsal root and trigeminal ganglia, and midbrain are noted at E17.5, E19.5, P1, and P5
(J:42478)
• at E16.7, mutant vestibular ganglia are significantly reduced, indicating a faster rate of vestibular ganglion neuron degeneration relative to spiral ganglion neurons
(J:43752)
• at E18.5, 34% of vestibular ganglion neurons are already lost via apoptosis
(J:43752)
• at E18.5 and P0, homozygotes show a 44%-68% increase in the number of TUNEL+ apoptotic cells in the vestibular ganglion
(J:43752)
• by P4, 77% of vestibular ganglion neurons are lost via apoptosis
(J:43752)
• at P7, 15% of vestibular ganglion neurons are lost
(J:82156)
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growth/size/body
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• homozygotes are viable but are 10-20% smaller than wild-type littermates
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reproductive system
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• homozygotes display reduced fertility
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homeostasis/metabolism
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• homozygotes exhibit higher energy expenditure than wild-type littermates
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cellular
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• at P7/P8, pillar cells remain undifferentiated almost throughout the cochlea
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