endocrine/exocrine glands
• reduced exocytosis in chromaffin cells when stimulated with 70mM potassium for 1 minute
• decreased amounts of catecholamine released for each fusion event involving vesicles and the cell membrane
• foot signals resulting from fusion pore formation decreased in height
• less neurotransmitter released per foot signal
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behavior/neurological
• mutants exhibit a deficit in non-spatial working memory, with mutants spending a lower percentage of time examining the novel object in the retention testing phase of a novel object recognition task
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• in the Morris water maze test, over 6 days of place discrimination training to learn the position of the submerged platform, mutants show slower escape latencies than wild-type mice
• when the hidden platform is removed and a probe trial is conducted on day 7 of a Morris water maze test, mutants spend less time in the target quadrant indicating that they did not learn the location of the platform
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• mutants do not display normal spontaneous alternation behavior in a Y-maze, indicating a deficit in short term memory
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• while mutants spend a similar amount of time in the novel arm of a Y-maze as do controls, they rear more than controls, indicating increased anxiety
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• mutants rear more times than controls in 30 min trials
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cellular
• 53.3% reduction in the number of ldU-labeled neurons within the dentate gyrus, indicating a reduction in the formation of new terminally differentiated neurons within the dentate gyrus in adults
• subventricular zone-derived neurospheres produce a higher proportion of astrocytes (85.91 vs. 75.93%) and oligodendrocytes (2.25 vs. 1.45%) than wild-type neurospheres
• ability of cultured neural progenitor cells to generate neurons is reduced (17.9 vs. 10.98%)
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nervous system
• 53.3% reduction in the number of ldU-labeled neurons within the dentate gyrus, indicating a reduction in the formation of new terminally differentiated neurons within the dentate gyrus in adults
• subventricular zone-derived neurospheres produce a higher proportion of astrocytes (85.91 vs. 75.93%) and oligodendrocytes (2.25 vs. 1.45%) than wild-type neurospheres
• ability of cultured neural progenitor cells to generate neurons is reduced (17.9 vs. 10.98%)
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• reduction in hippocampal volume
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• mutants show a trend towards a reduction in the total number and density of neurons in the CA1 region of the hippocampus
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• significant decrease in the size of the dentate gyrus, with a 33% reduction in volume
• 40% decrease in neurons in the dentate gyrus, however the density of neurons within the region is not different from wild-type
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• apical and basal dendrites of CA1 hippocampal pyramidal neurons exhibit a 39.2% and 28.8% decrease in spine density, respectively
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• reduction in the total number of neurons in the dentate gyrus and a trend towards a reduction of neurons in the CA1 region of the hippocampus
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• mutants exhibit a decrease is overall level of glutamate-evoked intracellular calcium in hippocampal neurons indicating impaired glutamate-evoked post-synaptic calcium transients
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• mutants fail to maintain long-term potentiation in hippocampal slices, showing a shorter average decay time constant and a reduction in the mean amplitude of responses to high frequency stimulation
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
Down syndrome | DOID:14250 |
OMIM:190685 |
J:184606 |