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.
Translational control by eIF4E regulates the synthesis of neuroligins, maintaining the excitation-to-inhibition balance, and its dysregulation engenders ASD-like phenotypes.
References
Type
Title
Author, Year
Primary
Autism-related deficits via dysregulated eIF4E-dependent translational control.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Exon 2 was replaced by a neomycin resistance cassette, disrupting amino acids 49-110, protein was found ot be absent from brain extracts.
Allele Type: Knockout
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Transgenic mice in which eIF-4E expression is driven by the ubiquitous beta-actin promoter, mice are also called betaT-Eif4e and have increased formation of tumors.
Allele Type: Transgenic
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
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
