behavior/neurological phenotype

• seizures
  • epileptic seizures in adults
  (MGI Ref ID J:202031)

nervous system phenotype

• abnormal brain morphology
  (MGI Ref ID J:91113)

• abnormal CNS synaptic transmission
  • inhibitory output of hilar mossy cells to granule cells is reduced in both pre-symptomatic and symptomatic mutants; 40Hz tetanic stimulation results in an increase in depression at inhibitory synapses in granule neurons, however it is similar to wild-type at excitatory synapses, and the ratio between the evoked excitatory and inhibitory responses on the same granule cell is increased for the last 10 responses of the train, with a decrease of inhibitory responses
  (MGI Ref ID J:202031)
  • reduction in synaptic activity in dentate gyrus mossy cells of young pre-symptomatic mutants
  (MGI Ref ID J:202031)
  • at excitatory synapses, and the ratio between the evoked excitatory and inhibitory responses on the same granule cell is increased for the last 10 responses of the train, with a decrease of inhibitory responses
  (MGI Ref ID J:202031)

• abnormal hippocampus physiology
  • hilus upon stimulation of the perforant path
  (MGI Ref ID J:202031)
  • pre-symptomatic mutants exhibit network impairments of the dentate gyrus, showing reduced mean amplitude of the response in the hilar region and a longer propagation time of evoked field postsynaptic potentials (fPSP), indicating decreased activity in the hilus upon stimulation of the perforant path
  (MGI Ref ID J:202031)
  • hilar mossy cells of both young pre-symptomatic and older symptomatic (4-6 months) mice exhibit decreased excitability, showing a lower firing rate, an increase in the rheobase, and reduced input resistance
  (MGI Ref ID J:202031)
  • Normal - however, granule cell excitability is normal
  (MGI Ref ID J:202031)

• abnormal synaptic vesicle number
  • the number of synaptic vesicles within the mossy fiber terminals in the hilar region of the dentate gyrate is reduced, however the total number of docked synaptic vesicles does not differ
  (MGI Ref ID J:202031)

• delayed CNS synapse formation
  • synapse formation is delayed 2-3 days in culture
  (MGI Ref ID J:91113)

• seizures
  • epileptic seizures in adults
  (MGI Ref ID J:202031)

• abnormal excitatory postsynaptic potential
  • pre-symptomatic mutants exhibit a longer propagation time of evoked field postsynaptic potentials in the hilar region of the dentate gyrus
  (MGI Ref ID J:202031)

• decreased synaptic depression
  • the depression induced by a train of stimuli (20 Hz for 5s) is reduced in hippocampal slices of young mutants, suggesting a reduced feedback inhibition of the granule cell layer
  (MGI Ref ID J:202031)

• decreased brain weight
  • at E16, brain weight was 17% lower than normal
  (MGI Ref ID J:91113)
  • by E19 the brain weight reduction was only 12%
  (MGI Ref ID J:91113)

• abnormal miniature excitatory postsynaptic currents
  • a decrease in excitatory presynaptic input on hilar mossy cells
  (MGI Ref ID J:202031)
  • hilar mossy cells of the dentate gyrus of both pre-symptomatic and symptomatic mutants show a reduction in miniature excitatory postsynaptic current (mEPSC) frequency and amplitude after blocking GABA receptors and NA+ channels with bicucalline indicating a decrease in excitatory presynaptic input on hilar mossy cells
  (MGI Ref ID J:202031)

• abnormal neuron morphology
  • neurons in culture are arrested in an undifferentiated stage prior to axon formation
  (MGI Ref ID J:91113)

mammalian phenotype

• taste/olfaction phenotype
  • Normal - olfaction is intact
  (MGI Ref ID J:201707)

behavior/neurological phenotype

• abnormal short term object recognition memory
  • in the social recognition test, adults spend a similar time in exploring the intruder mouse during all sessions and both young and adult mutants do not increase the exploration of the novel intruder mouse on the fifth session, indicating defective short-term social recognition
  (MGI Ref ID J:201707)
  • erm social recognition
  (MGI Ref ID J:201707)

• abnormal social investigation
  • in the resident-intruder test, mutants show reduced social interaction with the intruder mice after 1-2 months of social isolation
  (MGI Ref ID J:201707)
  • in the social novelty test, young and adult mutants do not discriminate between familiar and novel mice compared to controls that spend more time exploring the novel mouse than a familiar mouse
  (MGI Ref ID J:201707)
  • in a modified three-chamber social approach test, mutants exhibit reduced interest for both the social stimulus (unfamiliar stranger mouse) and the novel empty cup
  (MGI Ref ID J:201707)

• abnormal emotion/affect behavior
  • mutants bury fewer marbles than controls when placed in a cage with new bedding and marbles and this behavior is associated with reduced time spent in digging, whereas rearing behavior is unchanged
  (MGI Ref ID J:201707)
  • however, mutants exhibit normal anxiety related behaviors
  (MGI Ref ID J:201707)
  • after habituation to marbles, mutants still bury less marbles than controls, suggesting this behavior is no due to an altered response to novelty but a decrease in interest toward the environment
  (MGI Ref ID J:201707)

• increased aggression towards mice
  • in the social dominance tube test, adults show more dominant behavior than controls
  (MGI Ref ID J:201707)

• increased grooming behavior
  • young and adult mutants exhibit increased repetitive self-grooming behavior
  (MGI Ref ID J:201707)