Analysis Tools
behavior/neurological
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• homozygotes fail to respond to a hand clap
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• older homozygotes often roll onto their backs and flail their hind legs and tail while attempting to right themselves
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• young homozygotes fail to maintain their balance when walking or standing and frequently fall onto their sides
• by 5 months of age, homozygotes improve in their ability to maintain an upright position, and many tend to alternately hyperextend and clench their rear legs and feet
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abnormal gait
(
J:48863
)
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• homozygotes exhibit an unsteady gait
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hearing/vestibular/ear
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• at 5-6-weeks of age, homozygotes show a variable architecture ranging from a small tunnel of Corti with identifiable hair cells, pillar cells, and other cell types to complete absence of a tunnel or clearly identifiable support cells, pillar cells, or hair cells
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• at 5-6-weeks of age, the number of cochlear IHCs and OHCs is reduced in affected regions of the cochlear duct
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• at 5-6-weeks of age, cochlear IHCs and OHCs may be entirely absent in severely affected regions of the cochlear duct
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• at 5-6-weeks of age, the number of supporting cells may be reduced in affected regions of the cochlear duct
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• at 5-6-weeks of age, supporting cells may be entirely absent in severely affected regions of the cochlear duct
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• at 5-6-weeks of age, the number of pillar cells may be reduced or entirely absent in severely affected regions of the cochlear duct
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• at 5-6-weeks of age, the tunnel of Corti varies in regions of the cochlear duct from wide to greatly reduced or absent
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• homozygotes lack otoconia in both the saccule and utricle
• however, hair cells, support cells, and innervation of the sensory epithelium in the utricle and saccule are normal, and the otolithic membrane is present above the macula in each chamber
• in addition, the semicircular canals, and the crista ampullaris, with its sensory hair cells and gelatinous cupula within the ampulla of each duct, are normal
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• in organotypic cochlear cultures, the sensitivity of mechanoelectrical transduction channels to hair bundle displacement in outer cochlear hair cells is reduced
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• organotypic cultures of cochleae from P0-P3 mice (studied at P1-P4) indicate that, although the amplitude and kinetics of transduction currents in mutant OHCs obtained from the first row of the mid-apical turn are qualitatively similar to those of wild type controls, the curves relating bundle displacement (X) to channel opening probability, Popen (X) are shifted positively with respect to controls
• this shift is more pronounced in Atp2b2tm1Ges mice (175 nm) than in Atp2b2dfw mice (117 nm)
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• in organotypic utricular cultures from P0-P3 mice (studied at P1-P4), Ca2+ imaging of vestibular hair cells indicates that dissipation of stereociliary Ca2+ transients induced by Ca2+ uncaging is compromised
• as a result, the Ca2+ clearing rate of stereocilia is decreased and therefore similar to the slower rate of cell soma
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• wild-type mice show a typical ABR waveform at 40-70 db after exposure to a 0.1-ms broad band click; in contrast, all homozygotes fail to exhibit a detectable ABR waveform even at 99 db
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• at 4-6 months, homozygotes fail to produce any significant DPOAEs over a geometric-mean frequency range from 5.6-48.5 kHz compared with wild-type mice
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• at 5-6-weeks of age, homozygotes are profoundly deaf
(J:48863)
• homozygotes are congenitally and profoundly deaf
(J:108937)
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nervous system
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• at 5-6-weeks of age, the number of cochlear IHCs and OHCs is reduced in affected regions of the cochlear duct
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• at 5-6-weeks of age, cochlear IHCs and OHCs may be entirely absent in severely affected regions of the cochlear duct
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• in organotypic cochlear cultures, the sensitivity of mechanoelectrical transduction channels to hair bundle displacement in outer cochlear hair cells is reduced
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• organotypic cultures of cochleae from P0-P3 mice (studied at P1-P4) indicate that, although the amplitude and kinetics of transduction currents in mutant OHCs obtained from the first row of the mid-apical turn are qualitatively similar to those of wild type controls, the curves relating bundle displacement (X) to channel opening probability, Popen (X) are shifted positively with respect to controls
• this shift is more pronounced in Atp2b2tm1Ges mice (175 nm) than in Atp2b2dfw mice (117 nm)
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• in organotypic utricular cultures from P0-P3 mice (studied at P1-P4), Ca2+ imaging of vestibular hair cells indicates that dissipation of stereociliary Ca2+ transients induced by Ca2+ uncaging is compromised
• as a result, the Ca2+ clearing rate of stereocilia is decreased and therefore similar to the slower rate of cell soma
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• the numerical density of Purkinje cells is slightly increased
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• the numerical density of granule cells is decreased while the percentage of pyknotic granule cells is increased
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• in some regions of the cochlear duct, myelinated nerve fibers, and Schwann cells fill Rosenthal's canals but are reduced in number or absent in others
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growth/size/body
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• homozygotes exhibit a ~20-30% reduction in body weight relative to wild-type or heterozygous mice
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homeostasis/metabolism
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• in the inner ear, sensory hair cells show abnormal calcium homeostasis due to absence of otoconia
(J:108937)
• in organotypic utricular cultures from P0-P3 mice, Ca2+ imaging of vestibular hair cells indicates that dissipation of stereociliary Ca2+ transients induced by Ca2+ uncaging is compromised
(J:119503)
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