Analysis Tools
behavior/neurological
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• the time spent on the open arms of the elevated plus maze by homozygous mutant and wild-type mice is similar, indicating they experience similar anxiety levels
• performance in the Morris water maze is similar for homozygous mutant and wild-type mice, suggesting the mutation does not affect spatial learning or spatial memory
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• homozygous mutant mice exhibit disruption in latent inhibition (LI) of fear conditioning by pre-training exposure to the conditioned neutral stimulus (CS; sound) without the noxious unconditioned stimulus (US; shock)
• the antipsychotic clozapine does not restore LI in these mice
• mutant mice that are not not pre-exposed to the unpaired neutral stimulus acquire a strong US/CS association
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• in a working memory test using a discrete paired-trial variable-delay T-maze task, homozygous mutant mice make fewer correct choices than do wild-type mice at shorter (5 s and 10 s) but not longer (30 s) choice delay intervals
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• homozygous mutant mice consume significantly less of a 10% sucrose solution relative to water consumed than do wild-type mice, consistent with low reward responsiveness
• the ability of homozygous mutants to taste sweetness is unimpaired, as demonstrated by the similarity of mutants' and controls' preferences for various sucrose concentrations
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• in the forced swim test (FST), a test of depressive behavior, homozygous mutant mice spend significantly more time (p<0.05) than wild-type mice floating immobile; on day 2, heterozygous and wild-type mice also exhibit increased immobility, but homozygotes again spend significantly more time immobile
• although both bupropion and the phosphodiesterase 4 (PDE4) inhibitor rolipam diminish the immobility time of wild-type mice, only the antidepressant bupropion decreases the time homozygous mutant mice spend immobile
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• in the sociability test, whereas wild-type mice spend significantly more time in a chamber with an unfamiliar mouse than in an unoccupied chamber, neither homozygous nor heterozygous mutant mice show such a preference
• in the social novelty test, whereas wild-type mice spend more time in a chamber with a new unfamiliar mouse than with one to which they previously have been introduced, both homozygous and heterozygous mutant mice show no such preference
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nervous system
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• magnetic resonance imaging (MRI) reveals that the brain volumes of homozygous and heterozygous mutant mice are 6% lower than those of wild-type mice
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• MRI reveals contraction of the thalamus in homozygous and heterozygous mutant mice
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• MRI reveals contraction of the entorhinal cortex in homozygous and heterozygous mutant mice
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• MRI reveals contraction around the cerebral cortex, without alteration of white-matter tracts, in homozygous and heterozygous mutant mice
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• MRI reveals contraction of the cerebellum in homozygous and heterozygous mutant mice
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• mice homozygous for this mutation exhibit significantly lower prepulse inhibition (PPI; p<0.01), i.e., less reduction of the startle response following a prepulse, than do wild-type mice
• the antidepressant bupropion, a dopamine and norepinephrine reuptake inhibitor, abolishes the PPI deficit of homozygous mutants
• the typical antipsychotic haloperidol, a dopamine D2 receptor antagonist, fails to alleviate the PPI deficit in mice homozygous for this mutation
• the atypical antipsychotic clozapine, a combined dopamine D2 and serotonin receptor antagonist that increases PPI in wild-type mice, fails to alleviate the PPI deficit in homozygous mutant mice
• the phosphodiesterase 4 (PDE4) inhibitor rolipram does not affect the PPI in mice with this mutation
• in the absence of a prepulse, the amplitude of the acoustic startle response is similar in homozygous mutant and wild-type mice; the acoustic startle is unaffected by haloperidol, clozapine, bupropion or rolipram
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| melancholic depression | DOID:1595 |
OMIM:608516 |
J:120634 | |
