behavior/neurological
• mice show higher shock reactivity, with increased velocity immediately after the shocks and more freezing in response to the first tone-shock pairing indicating increased immediate, generalized, and conditioned fear responses to stressful events
• however, mice show a similar contextual fear conditioning the day after the training session
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• mice exhibit a neophobia-induced hypolocomotion such that when placed in the novel environment of the open field, they show inhibition of ambulatory activity restricted to the first minute of the test
• mice show a general decrease in locomotor activity in the elevated plus maze, with mice making fewer transitions between the two compartments of the light/dark box
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• in the resident-intruder test, mutant lactating females exhibit fierce aggression towards a harmless female intruder 4-5 days after parturition
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• in the resident-intruder test, mutant resident males are more aggressive towards intruders than wild-type littermates, with shorter first attack latency and higher number and duration of attacks
• mice treated with the anti-depressant fluoxetine show reduced aggression in the resident-intruder test
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• mice exhibit reduced preference for a sucrose solution, indicating anhedonia-like symptoms
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• males exhibit an increased depressive-like behavior in the repeated open-space force swim, with increased immobile water behavior compared to wild-type mice
• males do not respond to chronic fluoxetine treatment in the repeated open-space force swim (chronic stress)
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• mice show a higher latency to drink the reward in the novel environment compared to wild-type mice indicating anxiety-related behavior in the novelty-induced hypophagia test
• chronic fluoxetine treatment reduces the latency to drink the reward in the anxiogenic environment
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• mice exhibit impaired nesting behavior
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• males spend less time close to a partition that separates them from a receptive female and none show mounting behaviors when the receptive female is introduced into the home cage, indicating reduced sexual motivation
• males do not spend more time chemoinvestigating female-soiled bedding when presented simultaneously with male-soiled bedding or clean bedding as controls, indicating a deficit in female-directed behavior
• 3 of 8 males attack the female intruder when shes introduced into the home cage
• however, olfactory sense appears normal in the hidden cookie test
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• in the resident-intruder test, males show a reduction in social interaction, with males engaging rapidly and frequently in impulsive aggression without the normal investigatory and threatening sequence of acts and postures
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• males spend less time exploring a male stimulus mouse in a partition test
• however, males exhibit normal recognition of male-derived olfactory cues
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homeostasis/metabolism
• mice exhibit lower levels of the dopamine metabolites 3,4 dihydroxy-phenylacetic acid and homovanillic acid in the prefrontal cortex, indicating reduced dopaminergic activities
• mice exhibit lower levels of the serotonin metabolite 5-hydroxyindole acetic acid in the prefrontal cortex, indicating reduced serotonergic activities
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• slight decrease of serotonin in the hippocampus and the nucleus accumbens
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
major depressive disorder | DOID:1470 |
OMIM:608520 OMIM:608691 |
J:244400 |