Knockout of the EIF4EBP2 gene in mice results in an increased ratio of excitatory to inhibitory synaptic inputs and autistic-like behaviours (that is, social interaction deficits, altered communication and repetitive/stereotyped behaviours) (Gkogkas et al., 2012).
Molecular Function
This gene encodes a member of the eukaryotic translation initiation factor 4E binding protein family. The gene products of this family bind eIF4E and inhibit translation initiation. However, insulin and other growth factors can release this inhibition via a phosphorylation-dependent disruption of their binding to eIF4E. Regulation of protein production through these gene products have been implicated in cell proliferation, cell differentiation and viral infection.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Autism-related deficits via dysregulated eIF4E-dependent translational control.
Rescue Type:
RESCUE-Genetic
Rescue Paradigm:
EIF4BP2 homozygous KO were given a single injection of 3 ml of lentiviral particle 1.4E+7TU, containing small hairpin RNAs against Nlgn2 via brain-infusion (1mm rostral of the bregma and 2mm right of midline at a depth of 2 mm) .
Treatment does not improve measured phenotype (was expected to do so)
Ameliorated
Treatment provides partial correction or improvement of measured phenotype
No adverse effect
Treatment does not affect the parameter adversely
Sustained effect
Treatment has long term effect of restoration or amelioration, tested AFTER stopping administration (not applied for continuing long-term treatment) . Will be applied only where treatment has had restorative effects during administration or in the first battery of tests conducted.
No sustained effect
Treatment has no long term of restoration or amelioration detectable, after stopping administration. Will be applied only where treatment has had restorative effects during administration or in the first battery of tests conducted.
Description: Social interaction defect is exacerbated in terms of time spent with stranger mouse, interaction time, and number of entries into chamber
Exp Paradigm: Three chambered social interaction test
Description: Abnormal transporter amounts indicated by increase in vesicular glutamate transporter (vglut) than vesicular gaba transporter (vgat) puncta and protein amounts in ca1 dendritic layer of hippocampal slices Exp Paradigm: Wester blot analysis using hippocampal slices
Description: Increased amplitude and frequency of ampa receptor mediated miniature excitatory postsynaptic currents (mepsc) in pyramidal neurons Exp Paradigm: Whole cell recordings of hippocampal slices
Miniature post synaptic current amplitude: inhibitory1
Increased
Description: Increased mipsc's amplitude in gabaa synapses is seen in the eif4ebp2 null mice, Exp Paradigm: Whole cell recordings of hippocampal slices
Description: Decreased reciprocal social interaction indicated by shorter period of time spent interacting Exp Paradigm: Reciprocal social interaction test
Description: Decreased social approach indicated by significantly reduced time spent in stranger mouse compartment Exp Paradigm: Male mice: three chambered social arena test
Description: Increased ultrasonic vocalizations demonstrated by higher number of calls with a longer duration Exp Paradigm: Pup separation ultrasonic vocalizations
