The EIF4E transgenic mouse shows increased cap-dependent translation, synaptic abnormalities in the medial prefrontal cortex, striatum, and hippocampus, repetitive behaviors and deficits in social interactions. The cap-dependent translation inhibitor, 4EGI-1, rescues repetitive behaviors and deficits in social interactions in the EIF4E transgenic mutant mice.
References
Type
Title
Author, Year
Primary
Exaggerated translation causes synaptic and behavioural aberrations associated with autism.
Model Type:
Genetic
Model Genotype:
Other
Mutation:
Transgenic mice were generated using a minigene cassette consisting of the human EIF4E cDNA, the ubiquitous human actin promoter, and the SV40 polyadenylation site. eIF4E transgenic mice show increased expression of eIF4E in multiple brain regions including the prefrontal cortex, striatum, hippocampus and cerebral cortex.
Allele Type: Overexpression (Transgenic)
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Other
Mutation:
Cx3cr1^CreER/+;Rosa26^Ai9/+ mice mice with conditional overexpression of translation initiation factor eIF4E allele at the Rosa26 locus, inserted between exons 1 and 2, that expresses Myc-tagged eIF4E (R26Eif4e) in a Cre-dependent manner in microglia (using Cx3cr1^CreER, Jackson Laboratories stock no. 021160). One tamoxifen injection (180 mg/kg, s.c.) was administered to Cx3cr1^CreER/+;Rosa26^Ai9/+ mice at P0 to activate CreER to excise the loxP-flanked transcription blocker of the Rosa26Ai9 allele in microglia, leading to tdTomato expression. CD68-EGFP transgene reporter is used to assay microglial migration.
Allele Type: Overexpression (Transgenic)
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: NA
Mutant ES Cell Line: NA
Model Source: NA
Model Type:
Genetic
Model Genotype:
Other
Mutation:
Mice with conditional overexpression of translation initiation factor eIF4E allele at the Rosa26 locus, inserted between exons 1 and 2, that expresses Myc-tagged eIF4E (R26Eif4e) in a Cre-dependent manner in neurons (using Syn1-Cre, Jackson Laboratories stock no. 003966), from embryonic day 12.5 onwards. (Syn1-Cre;R26^Eif4e/Eif4e, NN^4E).
Allele Type: Overexpression (Transgenic)
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: NA
Mutant ES Cell Line: NA
Model Source: NA
Model Type:
Genetic
Model Genotype:
Other
Mutation:
Mice with conditional overexpression of translation initiation factor eIF4E allele at the Rosa26 locus, inserted between exons 1 and 2, that expresses Myc-tagged eIF4E (R26Eif4e) in a Cre-dependent manner in astrocytes, using GFAP-Cre (Jackson Laboratories stock no. 024098) which becomes active during late embryogenesis and the first postnatal week (GFAP-Cre;R26^Eif4e/Eif4e)
Allele Type: Overexpression (Transgenic)
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: NA
Mutant ES Cell Line: NA
Model Source: NA
Description: Eif4e transgenic mice show slight increase in total time spent moving and total distance travelled compared to controls
Exp Paradigm: Males only
Description: Eif4e transgenic mice show slight increase in total time spent moving and total distance travelled compared to controls
Exp Paradigm: Males only
Description: Eif4e transgenic mice show increased dendritic spine density and a smaller spine volume compared to controls
Exp Paradigm: Dendritic spines were imaged using two-photon laser-scanning microscopy. males only.
Spontaneous post synaptic event frequency: excitatory currents1
Increased
Description: Eif4e transgenic mice show an increase in the frequency but not amplitude of spontaneous synaptic excitatory mepsc events in layers ii/iii of acute mpfc slices, compared to controls. no changes were observed in layer v.
Exp Paradigm: Males only
Spontaneous post synaptic event amplitude: inhibitory currents1
Increased
Description: Eif4e transgenic mice show an increase in the amplitude, but not frequency, of inhibitory mipsc events in layers ii/iii of acute mpfc slices, compared to controls. no changes were observed in layer v.
Exp Paradigm: Males only
Description: Eif4e transgenic mice show reduced preference for a novel stranger compared to a novel inanimate object, compared to controls
Exp Paradigm: Males only.
Description: Eif4e transgenic mice show preference for a novel inanimate object over a stranger mouse, compared to controls
Exp Paradigm: Novel object interaction test. males only.
Description: Eif4e transgenic mice did not exhibit a significant reduction in freezing responses following extinction training as did control mice
Exp Paradigm: Males only
Description: Eif4e transgenic mice exhibited cognitive inflexibility in being impaired in locating the new platform positions compared to control mice
Exp Paradigm: Males only-water y-maze
Description: Eif4e transgenic mice exhibited cognitive inflexibility in being impaired in locating the new platform positions compared to control mice
Exp Paradigm: Males only- morris water maze test
Description: Eif4e transgenic mice show increased binding of eif4e to eif4g in the brain, compared to controls
Exp Paradigm: Transgenic brain tissue was used as sample. males only.
Description: Eif4e transgenic mice show increased expression of eif4e in multiple brain regions including the prefrontal cortex, striatum, hippocampus and cerebral cortex, compared to controls
Exp Paradigm: Males only
Description: Eif4e transgenic mice show increased de novo cap-dependent translation in the brain, compared to controls
Exp Paradigm: Puromycin was infused into the lateral ventricle of cannulated mice and newly synthesized proteins were labeled using sunset and de novo cap-dependent translation was observed. males only.
Description: Increase in microglia numbers in the mpfc, hip and str at 2 weeks; decrease in microglial numbers in the str at 6 weeks; no change in microglial density in the in the mpfc and hip at 6 weeks
Exp Paradigm: Iba1
Description: Higher spine density in mpfc at 6 weeks, increased spine density in pyramidal neurons of mpfc layer 5 and hippocampal ca1 at 2 and 6 weeks male but not female mice
Exp Paradigm: NA
Description: Downregulation of transcripts including markers for homeostatic microglia such as p2ry12, p2ry13, cx3cr1, tmem119, and slco2b1 associated with leukocyte cellcell adhesion, leukocyte migration, and cellcell adhesion
Exp Paradigm: NA
Description: Upregulation of genes associated with antimicrobial activity in the kegg pathway including pathways responding to herpes simplex infection, implicated in asd; no change of transcript level is seen at 6 weeks
Exp Paradigm: NA
Description: Upregulation of genes associated with autoimmune thyroid disease pathways, implicated in asd; no change of transcript level is seen at 6 weeks
Exp Paradigm: NA
Description: Upregulation of very few genes associated with polarized microglial states m1 (proinflammatory) and m2 (anti-inflammatory)
Exp Paradigm: NA
