Analysis Tools
mortality/aging
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• severe seizures can result in fatalities at 6 months or later
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behavior/neurological
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• mice exhibit autism-like behaviors including reduced social interaction, increased repetitive self-grooming, and deficits in communication and in learning and memory
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• on day 2, mice show a significant deficit in hippocampal-based, contextual fear memory with an increase in the motion index and a decrease in the time spent freezing (%) across trial blocks relative to wild-type controls
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• mice show a significant deficit in amygdala-dependent, cued fear memory with no significant change in the time spent freezing (%) after playing the cue (tone) relative to their pretone (baseline) activity
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• in the Barnes maze spatial memory test, mice are slower to use direct searches to find the target escape hole relative to wild-type controls, but do make progress in making more direct searches over the training sessions
• although mice use increasingly more direct searches during training, they still use serial searches significantly more than wild-type controls
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• in the 5 day probe of the Barnes maze test, mice show impaired memory of the escape hole location with significantly less nose pokes at the target and adjacent holes and a broader search of the board than wild-type controls
• mice take significantly longer to find the target hole and travel much longer before making an initial nose poke at the target hole than wild-type controls in both the 24 hour and the 5 day tests
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• in the open-field test, mice spend significantly less time in the center than wild-type controls, suggesting increased anxiety
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• adult mice bury significantly fewer marbles than wild-type control across all time points during a 25 min observation period, suggesting a reduced interest in the external environment
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• mice exhibit a ~3-fold increase in the time spent self-grooming and in the number of grooming episodes
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• in the open-field test, mice show significantly increased total track lengths and mean velocities relative to wild-type controls
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• mice show increased repetitive self-grooming behavior
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• in the 3-chamber social task, mice spend significantly less time interacting with a stranger mouse (Mouse 1) compared with the empty cage; the preference index for Mouse 1 is significantly decreased, indicating impaired sociability
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• in the 3-chamber social task, mice show no preference for a second mouse (Novel Mouse) placed into the remaining empty chamber opposite to Mouse 1; the preference index for Novel Mouse vs Mouse 1 is significantly decreased, indicating reduced interest in social novelty
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• ultrasonic vocalizations (USVs) are generally simpler with significantly more short and flat calls and fewer modulated and multiple jump calls relative to those made by wild-type controls, suggesting impaired communication
• however, no significant changes in average peak amplitude or peak frequency are observed at any point
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• mean call syllable duration and total time spent calling are significantly reduced at all developmental time points tested
• analysis of USVs revealed a significant reduction in the total number of calls at P5, P7 and P9, as well as fewer calls emitted within each minute of the 5 min recording period at each developmental time point
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• mice begin to exhibit severe seizures as early as 3 months of age, typically in response to animal handling; most seizures begin at >4 months
• some seizures result in fatalities at 6 months or later
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nervous system
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• mice begin to exhibit severe seizures as early as 3 months of age, typically in response to animal handling; most seizures begin at >4 months
• some seizures result in fatalities at 6 months or later
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• hippocampal and cortical brain lysates show a significant decrease in the protein expression of AMPAR subunit GluA1, the GABAAreceptor alpha1 subunit, and the inhibitory synaptic scaffolding protein gephyrin, with no changes in PSD-95 or synapsin expression
• immunostaining confirmed a marked decrease in total GluA1 staining intensity in P0 hippocampal brain slices
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• at P90, hippocampal pyramidal neurons show a 35% reduction in the density of dendritic protrusions relative to wild-type neurons
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• at P90, hippocampal pyramidal neurons show a 33% increase in the average length of dendritic protrusions relative to wild-type neurons
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• at P90, hippocampal pyramidal neurons show significantly less stubby spines relative to wild-type neurons
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• at P90, hippocampal pyramidal neurons show a significant increase in filopodia and thin protrusions relative to wild-type neurons
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• at P90, hippocampal pyramidal neurons show a significant increase in filopodia and thin protrusions with less stubby spines (indicating a reduction in mature spines), a 35% reduction in the density of dendritic protrusions and a 33% increase in the average length of protrusions relative to wild-type neurons
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• in acute hippocampal slices, paired-pulse ratio is markedly higher than in wild-type controls, esp. at high-frequency stimulation, indicating abnormalities in presynaptic function
• analysis of the input/output relationship at CA3-CA1 synapses revealed a reduction in excitatory synaptic strength, indicating reduced basal synaptic transmission
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• fEPSP recordings from hippocampal brain slices revealed an increase in paired-pulse facilitation
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integument
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• mice exhibit patches of fur loss due to excessive repetitive self-grooming behavior in the same body areas
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• when grouped-housed with wild-type controls, mice display fur loss on the chest
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| autism spectrum disorder | DOID:0060041 | J:283395 | ||
| non-syndromic X-linked intellectual disability 98 | DOID:0112044 |
OMIM:300912 |
J:283395 | |
