behavior/neurological
• in a fear conditioning test, mice show robust freezing behavior associated with contextual fear indicating enhanced contextual fear memory retention
• however, mice do not show abnormalities in olfaction or nocicpetion, locomotion, spontaneous motor activities in home cages, motor coordination, or anxiety-related tasks
|
• in the Morris water maze test, mice reach the hidden platform faster than wild-type mice in the second probe test indicating enhanced spatial learning
|
• mice show enhanced freezing behavior in a fear conditioning test
|
• mice exhibit enhanced startle response to an acoustic stimulus at 120 dB
|
• mice exhibit excessive repetitive wheel-running
• mutant mice bury more marbles than wild-type mice, however digging behavior during the reciprocal social interaction test is normal, indicating that increased burying behavior is due to higher sensitivity to marbles
|
• mice show reduced social investigation such as approach and sniffing and less physical contact with a male mouse in reciprocal social interaction test
• mice do not show a preference in terms of either time spent in each chamber or number of contacts with the strangers cage in a 3-chambered social approach test
|
• mice often hide under bedding material instead of social investigation
• social avoidance behavior such as freezing, escaping, and hiding is increased in time compared to wild-type mice
|
• mature males encountering estrous females emit fewer ultrasonic vocalizations -than wild-type males
• however, isolated nursing infants do not show differences from wild-type in ultrasonic vocalizations
|
growth/size/body
weight loss
(
J:241916
)
• mild, 6-9%, body weight loss at 8 weeks of age when mice are housed in a conventional group housing environment of 4-5 mice per cage, with body weight difference starting at 6 weeks of age and becoming obvious at 7-10 weeks
• however, no body weight loss is seen when mice are reared in an isolated housing condition from 3 weeks of age
|
nervous system
• excitatory postsynaptic protein PSD-95 is decreased and GluN2A is increased in the hippocampus of 8 week old mice
• lower basal synaptic expression of GluA1-containing AMPAR in the hippocampus
|
• slight but significant decrease in number of total spine-like protrusions on the apical dendrites of dorsal CA1 neurons
• increase in the number of oddly shaped spines with thin protrusions from the spine heads on the apical dendrites of dorsal CA1 neurons
• mean length of spines is longer on each dorsal CA1 neuron and the mean head width of spines is smaller
|
• cultured hippocampal neurons show increased total dendritic length and branching complexity
|
• the ratio of perforated synapses to total asymmetrical synapses is increased in the CA1 radial layer of the dorsal hippocampus
• synapses are structurally and functionally immature
|
• reduction in postsynaptic density length, wider synaptic clefts and increase in perforated postsynaptic density synapses, however, postsynaptic density thickness is not changed
|
• synaptic plasticity is enhanced
|
• mice exhibit an increase in silent synapses (excitatory synapses that have become non-functional at normal resting potential) in the hippocampus
|
• mice show lower ratio of AMPAR- to NMDAR-mediated excitatory postsynaptic currents of CA1 pyramidal neurons
|
• long term potentiation (LTP) of field excitatory postsynaptic potentials at Schaffer collateral/CA1 synapses is enhanced
• however, no differences are seen for either the paired-pulse or post-tetanic potentiation ratio, indicating that transmitter release is normal
|
• mEPSC frequency is reduced in the hippocampus
|
• prepulse inhibition of the auditory startle response is decreased
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
autism spectrum disorder | DOID:0060041 | J:241916 |