Mouse Genome Informatics
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    Eif4ebp2tm1Klan/Eif4ebp2tm1Klan
B6.129S4(C)-Eif4ebp2tm1Klan
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
behavior/neurological
• mutants display longer bouts and total duration of self-grooming
• mutant mice show a significant reduction in long-term memory for the context
• associative learning and short-term memory are normal
• in the hidden platform version of the Morris water maze, mutant mice exhibit a spatial learning impairment
• mutant mice show compromised spatial memory
• visual acuity, swimming ability, or motivation to escape from the water are not affected
• mutants bury more marbles than wild-type mice in the marble-burying test assessing stereotyped/repetitive behaviors
• mutants exhibit impaired social approach behavior, showing a reduction in time spent in the social (stranger1) compartment and decrease interaction time with stranger1, indicating a lack of preference for the social stimulus
• mutants exhibit a reduction in preference for social novelty, spending less time in the social novelty (stranger 2) compartment than wild-type mice
• in reciprocal social interaction tests, mutants interact for a shorter period of time with either other mutants or wild-type mice compared to wild-type mice interacting with wild-type mice
• in reciprocal social interaction tests, mutants initiate fewer contacts with other mutants
• treatment with 4EGI-1, a selective inhibitor which prevents Eif4e binding to Eif4g, rescues the excitatory/inhibitory synaptic activity imbalance and social deficits of mutants
• however, mutants exhibit normal behavior in the elevated plus maze test using the three-chamber social approach test, indicating normal anxiety levels
• pups emit a higher number of calls with a longer duration at P2-P12 compared to wild-type pups, indicating enhanced ultrasonic vocalizations
• peak amplitude of ultrasonic vocalizations is higher on P8 and P12

nervous system
• larger increase in vesicular glutamate transporter than vesicular GABA transporter puncta and protein amounts in the CA1 dendritic layer of the hippocampus
• spine density is increased in CA1 pyramidal cell dendrites
• mutants exhibit an increased ratio of excitatory to inhibitory synaptic inputs
• treatment with 4EGI-1, a selective inhibitor which prevents Eif4e binding to Eif4g, rescues the excitatory/inhibitory synaptic activity imbalance and social deficits of mutants
• minimal stimulation-evoked EPSCs and IPSCs from CA1 pyramidal neurons show an increase in both EPSC and IPSC amplitude, but no change in paired-pulse ratio
• minimal stimulation-evoked EPSCs and IPSCs from CA1 pyramidal neurons show an increase in both EPSC and IPSC amplitude, but no change in paired-pulse ratio
• in brain slice, mutants convert early-phase long term potentiation in the Schaffer collateral pathway
• there is a critical limit for activity induced translation
• alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor mediated miniature excitatory postsynaptic currents (mEPSCs) are increased both in amplitude and frequency in pyramidal neurons of mutants relative to wild-type mice
• the total synaptic charge transfer is increased for both mEPSCs and mIPSCs in pyramidal cells, however, the normalized increase of total charge transfer relative to wild-type mice is significantly larger for mEPSCs than for mIPSCs, indicating that excitation is increased to a larger extent than inhibition
• GABA(A) receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) are greater in amplitude, but not in frequency, in pyramidal cells of mutants compared to wild-type mice

Mouse Models of Human Disease
OMIM IDRef(s)
Autism 209850 J:194221