Phenotypes Associated with This Genotype

Genotype
MGI:3610950

• Allelic Composition: Eif4ebp2^tm1Klan/Eif4ebp2^tm1Klan
• Genetic Background: B6.129S4(C)-Eif4ebp2^tm1Klan

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

abnormal associative learning ( J:102163 )

• mutant mice show a significant reduction in long-term memory for the context

• associative learning and short-term memory are normal

abnormal spatial learning ( J:102163 )

• 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

increased grooming behavior ( J:194221 )

• mutants display longer bouts and total duration of self-grooming

increased stereotypic behavior ( J:194221 )

• mutants bury more marbles than wild-type mice in the marble-burying test assessing stereotyped/repetitive behaviors

abnormal social investigation ( J:194221 )

• 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

abnormal vocalization ( J:194221 )

• 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

abnormal hippocampus CA1 region morphology ( J:194221 )

• larger increase in vesicular glutamate transporter than vesicular GABA transporter puncta and protein amounts in the CA1 dendritic layer of the hippocampus

abnormal hippocampus pyramidal cell morphology ( J:194221 )

• spine density is increased in CA1 pyramidal cell dendrites

abnormal CNS synaptic transmission ( J:194221 )

• 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

increased excitatory postsynaptic current amplitude ( J:194221 )

• 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

abnormal inhibitory postsynaptic currents ( J:194221 )

• 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

abnormal long-term potentiation ( J:102163 )

• in brain slice, mutants convert early-phase long term potentiation in the Schaffer collateral pathway

• there is a critical limit for activity induced translation

abnormal miniature excitatory postsynaptic currents ( J:194221 )

• 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

increased miniature excitatory postsynaptic current amplitude ( J:194221 )

• alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor mediated miniature excitatory postsynaptic currents (mEPSCs) are increased in amplitude in pyramidal neurons of mutants relative to wild-type mice

increased miniature excitatory postsynaptic current frequency ( J:194221 )

• alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor mediated miniature excitatory postsynaptic currents (mEPSCs) are increased in frequency in pyramidal neurons of mutants relative to wild-type mice

increased miniature inhibitory postsynaptic current amplitude ( J:194221 )

• 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		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:194221