growth/size/body
• adult homozygotes have a body weight that is ~85% of that in wild-type controls
• however, adult brain and hippocampus weights remain normal
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behavior/neurological
N |
• homozygotes show no significant differences in their sensory abilities (hot plate test), neuromuscular strength (forelimb grip strength in Newton), vertical activity and stereotypic behavior relative to wild-type controls
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• in a T-maze alteration test, homozygotes show a significantly lower % of correct responses than wild-type controls at the certain blocks of 3 sessions during repetitive sessions with a short delay period (3 s)
• when task difficulty is raised by prolonging the delay period (>30 s), homozygotes show lower performances, suggesting a mild deficit in working memory
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• in the elevated plus maze test, homozygotes show a 1.43-fold longer travel distance, enter 1.82-fold more frequently into the open arms, and spend 2.21-fold longer time in the open arms than wild-type controls
• in the open field test, homozygotes spend significantly more time than wild-type controls in the center area of the apparatus during the first 60 min of the test
• in the light/dark transition test, homozygotes travel 1.54- and 1.34-fold longer distances than wild-type controls in the light and dark boxes, respectively, show a 1.62-fold increase in the number of transitions between dark and light boxes, and tend to spend more time in the light box than wild-type controls
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• homozygotes show a markedly short latency in the wire hang test and a significantly shorter latency to fall from the rotating drum in a Rotarod test
• however, homozygotes improve their performance during repeating trials of the Rotarod test in a manner similar to that of wild-type controls
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• in the home cage, homozygotes show significantly higher locomotor activity during night time than wild-type controls
• in the open field test, homozygotes show >1.5 times higher locomotor/exploratory activity than wild-type controls throughout the 120 min observation period
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• in the social interaction test in a new environment, the total duration of contacts and the mean duration per contact are 61% and 50% less than those of wild-type controls, respectively, suggesting poor social interaction
• however, homozygotes showed a normal physical contact pattern in the home cage
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nervous system
• analysis of neuronal differentiation of BrdU-incorporated cells suggests that excess newborn neurons in the subgranular zone (SGZ) of the dentate gyrus continue to differentiate to some extent (i.e. to doublecortin-positive immature neurons) until 2 weeks after their birth, but fail to differentiate further or survive thereafter
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• homozygotes show a 1.65-fold increase in the number of parvalbumin expressing interneurons in the hippocampal CA1 subregion relative to wild-type controls
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• homozygotes show a 1.65-fold increase in the number of parvalbumin expressing interneurons in the hippocampal CA1 subregion relative to wild-type controls
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• homozygotes show increased adult neurogenesis in the subgranular zone (SGZ) of the dentate gyrus resulting in a more immature neuronal population in the granule cell layer
• at 7 and 8 weeks of age, the average number of BrdU-positive cells per section in the SGZ is 1.65- and 1.94-fold greater than in wild-type controls, respectively, with a similar increase noted for Ki-67-positive cells
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• at 7 weeks of age, staining of doublecortin (a marker for neuroblast and immature neurons) is stronger in the mutant dentate gyrus than that in wild-type controls
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homeostasis/metabolism
N |
• homozygotes exhibit normal body temperature
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cellular
• analysis of neuronal differentiation of BrdU-incorporated cells suggests that excess newborn neurons in the subgranular zone (SGZ) of the dentate gyrus continue to differentiate to some extent (i.e. to doublecortin-positive immature neurons) until 2 weeks after their birth, but fail to differentiate further or survive thereafter
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skeleton
N |
• homozygotes exhibit a normal skeleton
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