mortality/aging
• homozygous progeny are observed in lower numbers than expected from heterozygous intercrosses
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growth/size/body
• between 2 and 6 weeks, reduced body size of homozygotes compared to littermates is observed, despite no differences in daily food intake; by 7 weeks of age, mice weigh 90% of control littermates
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behavior/neurological
• mice are unable to distinguish between a novel and familiar object, indicating impaired nonspatial learning/memory
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• homozygous mice show impaired spatial learning/memory in a hidden platform swim test
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• null mice spend more time in center of open field compared to controls; in elevated zero maze, homozygotes spend 41% of time in open areas compared to 12 or 14% for wild-type or heterozygous mice
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• on balance beam, mutants travel 198 cm compared to 568 or 439 cm for wild-type or heterozygous littermates
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• mice fall off rotating rod with latency of ~43 seconds compared to 114 and 93 seconds for wild-type and heterozygous mice; mice cannot compensate for this with training
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nervous system
• growth cones of E18 hippocampal neurons appear more 'spiky' and elongated than wild-type growth cones; roundness index of mutant growth cones is 5.3 compared to wild-type score of 4.3
• in vivo, CA1 hipoocampal and cortical neurons in 10-week old mice show a reduction in dendritic spine density (104 spines/100 um or 99 spines/100 um in wild-type hippocampal or cortical (layer 1) neurons compared to 89 spines/100 um or 79.8 spines/100 um in mutant hippocampal or cortical neurons)
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• cultured E18 hippocampal neurons show 60.1% less neurite outgrowth (sum of axonal and dendrite length) than wild-type neurons after 5 days
• leading edge of growth cone rarely extended to tips of filopodia
• lamellipodia extend at rate of 6.85 um/minute compared to 5.84 um/minute observed in wild-type cultured neurons, but retraction velocity is similar for both genotypes
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• hippocampal slices from mutants display a 29% reduction in maximal fEPSPs
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• NMDAR to AMPA receptor fEPSP ratio is significantly higher in null neurons
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• early phase of LTP is increased relative to wild-type (seen in responses from 0-60 minutes)
• L-LTP induced by rapid theta bursts results in modest increase in potentiation at 150-180 minutes
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• LTD is reduced relative to wild-type (seen in responses from 0-60 minutes)
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