mortality/aging
• most double homozygous mutant mice died around day 12
• the lifespan of double-mutant mice increased by several days when healthy littermates were removed at day 7
• with continuous nursing with wetted food twice daily, four double mutant mice survived the weaning period up to 50 days old
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growth/size/body
• apparent growth impairment by day 7
• double homozygous mutant mice that survived the weaning period at 50 days old weighed less than half of the expected body weight
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behavior/neurological
• double homozygous mutant mice that survived the weaning period demonstrated a mild unusual tremor and subtle rear limb spasticity
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• double homozygous mutant mice that survived the weaning period swayed backwards while grooming and used their tail for balance
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• double homozygous mutant mice that survived the weaning period demonstrated hesitating voluntary movements
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nervous system
• neuronal loss was paralleled by an increasing occurrence of hypertrophic astrocytes and Bergmann glia
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• widespread TUNEL-positive staining in cerebral cortex and the cerebellar granule cell layer in brains of P23.5-24.5 mutant mice
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• the CA3 region of the stratum pyramidale was broadened and split
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• 50 days old mice exhibited pronounced cerebral and cerebellar atrophy
• molecular and internal granule cell layer were reduced and the Purkinje-cell layer had disappeared due to massive neuronal death in the cerebellar Purkinje- and granule-cell layers and the cerebral cortex during the third and fourth week of life
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integument
• hyperproliferation of keratinocytes
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cellular
• neuronal loss was paralleled by an increasing occurrence of hypertrophic astrocytes and Bergmann glia
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• widespread TUNEL-positive staining in cerebral cortex and the cerebellar granule cell layer in brains of P23.5-24.5 mutant mice
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