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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• vestibular sensory epithelia show a variable degree of innervation by both afferent and efferent fibers
• inner ears show an anterior to posterior gradient of fiber loss, with the posterior vertical semicircular canal being most affected and the anterior vertical canal relatively unaffected
• the density of fibers in the saccule and utricle is only slightly reduced relative to wild-type
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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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• vestibular sensory epithelia show a variable degree of innervation by both afferent and efferent fibers
• inner ears show an anterior to posterior gradient of fiber loss, with the posterior vertical semicircular canal being most affected and the anterior vertical canal relatively unaffected
• the density of fibers in the saccule and utricle is only slightly reduced relative to wild-type
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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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• 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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