Analysis Tools
behavior/neurological
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• while awake, rescued mice walk continuously without pausing or resting
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• rescued mice fail to balance themselves and fall down 8-10 times per minute while waliking
• when placed on a 3 cm-wide platform, rescued mice fall over, whereas control transgenic mice stay balanced for >5 min
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growth/size/body
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• at P30, ND-/-Tg mice show a significant reduction in body weight relative to control transgenic mice
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• rescued mice (ND-/-Tg) survive to adulthood but exhibit a slower growth rate compared to control transgenic mice
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hearing/vestibular/ear
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• homozygotes display normal differentiation of hair cells in the entire sensory epithelium
• no ultrastructural changes are detected in mutant semicircular canal hairs
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• at P0, the volume of the modiolus and the radius of the mutant cochlea are severely reduced
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• in homozygotes, the cochlear sensory epithelium appears to be shorther than normal
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• homozygotes exhibit normal somatosensory evoked potentials but completely lack auditory evoked potentials
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nervous system
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• rescued ND-/-Tg mice display impaired postnatal neurogenesis due to a neuronal deficit in the granule layers of the cerebellum and hippocampus
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• at P30, all major cerebellar lobules are identifiable but show a shallow foliation pattern
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• at P6, the cerebellum of rescued mice shows reduced EGL thickness in the posterior lobules
• at P6, anterior lobules contain the normal 8- to 10-cell thick layer of EGL, whereeas posterior lobules have a thinner EGL of only 4- to 5-cell thickness
• at P0, numerous apoptotic cells are detected in the posterior lobules of cerebellar cortex in the inner EGL
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• at P30, brains of ND-/-Tg mice lack a recognizable dentate gyrus
• the absence of DG formation becomes apparent as early as E18.5
• in contrast, formation of the Ammon's horn remains unaffected
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• at P30, Purkinje cells display an abnormal arrangement in the posterior lobules of the cerebellum and fail to form a monolayer
• little variation in the number of Purkinje cells is observed along the anteroposterior (A-P) axis
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• at P30, ND-/-Tg mice exhibit a slight decrease in cerebellar Purkinje cell number
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• at P30, numerous apoptotic cells are detected the remaining anterior IGL cells; however, at P88, ~5%-10% of granule cells are still detectable in the anterior cerebellum
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• at P30, ND-/-Tg mice show a 30%-40% reduction in the size of the cerebellum
• the overall size reduction becomes evident at P2
• in contrast, the size of the cerebrum and olfactory bulbs appears normal
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• in homozygotes, vestibular sensory epithelia show a variable degree of innervation by both afferent and efferent fibers
• in the inner ear, mutants display an anterior to posterior gradient of fiber loss, with the posterior vertical semicircular canal being the most affected and the anterior vertical canal being relatively unaffected
• the density of fibers in the mutant saccule and utricle is only slightly reduced relative to wild-type
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• homozygotes show a significant reduction in the number of vestibulocochlear ganglion cells as early as E10.5
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• homozygotes exhibit a severe depletion of inner ear sensory neurons during development
• neuronal loss and the pattern of remaining sensory neurons and afferent innervation reach their final configuration by E14.5
• surviving vestibular and spiral sensory neurons persist up to 9 months of age
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• by E14.5, the spiral (cochlear) ganglion is almost absent
• at P0, most of the surviving spiral ganglion cells are abnormally located in the middle turn of the cochlea, inside or close to the modiolus
• homozygotes display a high degree of variation in the density of the remaining afferent and efferent fibers
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• at P0, the volume of mutant vestibular ganglia is significantly decreased
• at P0, mutant vestibular ganglia display a migration defect and are mislocated inside the otic capsule
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cellular
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• rescued ND-/-Tg mice display impaired postnatal neurogenesis due to a neuronal deficit in the granule layers of the cerebellum and hippocampus
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