behavior/neurological
N |
• at 6-8 months of age, homozygotes display normal motor coordination, balance, and fine motor control of the forelimbs relative to wild-type littermates
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• in the Morris water maze test, homozygotes exhibit shorter escape latencies than wild-type littermates
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• homozygotes exhibit a prolonged latency in the tail-flick assay relative to wild-type littermates, suggesting hyporesponsiveness to tactile stimuli
• in contrast, the % of maximum electrical shock level (0.08 mA) required to elicit running and vocalization is significantly lower in mutant mice, indicating an increase in shock sensitivity relative to wild-type mice
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hyperactivity
(
J:85927
)
• homozygotes exhibit an increased number of movements relative to wild-type littermates, as detected with infrared monitors during a 30 min session
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nervous system
• homozygotes display enhanced LTP in the dentate gyrus of the hippocampus, as shown by an increase in the average potentiation of the fEPSP slope at 60 min after tetanic stimulation
• notably, LTP in CA1 pyramidal cells (induced by tetanic stimulation of Schaffer collaterals) appears unchanged, and basic synaptic transmission and paired pulse facilitation remain relatively normal
• enhanced LTP coincides with a decrease in the transient Kv4 channel-dependent A-type current and can be mimicked in wild-type mice by phrixotoxin-2 (a Kv4 channel blocker)
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• homozygotes display a significant decrease in the Kv4 channel-dependent transient A-type current from dentate gyrus granule cells
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homeostasis/metabolism
• in the cerebellum, homozygotes exhibit a ~50% reduction in the levels of both Abeta40 and Abeta42 peptides relative to wild-type littermates, indicating an effect on presenilin-dependent gamma-secretase cleavage in vivo
• in the cortex, Abeta40 peptide levels are reduced to a lesser extent while Abeta42 levels remain unaffected
• Abeta peptide levels display a trend toward reduction in the hippocampus
• however, changes in Abeta levels are not associated with any detectable changes in amyloid protein precursor (APP) processing
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