Eif4ebp2 (4E-BP2) knock-out mice exhibit impaired spatial learning, memory deficits, autistic-like behavior and enhanced glucose tolerance. They are suitable for use in applications related to the study of the mTORC1 pathway, regulation of the eukaryotic initiation factor 4F (eIF4F) complex, glucose homeostasis, sarcopenia (loss of muscle mass and function due to aging process), and autism spectrum disorders.
Nahum Sonenberg, McGill University
The targeted Eif4ebp2 gene encodes a translation repressor protein that binds the eukaryotic translation initiation factor 4E (eIF4E) and is highly expressed in brain. These 4E-BP2 knock-out mice carry an allele in which a neo cassette has replaced exon 2, encoding amino acids 49-110. Mice that are homozygous for the targeted mutation are viable and fertile. No gene product (protein) is detected by western blot analysis of cerebellum, cortex and hippocampus extracts from homozygotes. The enhanced glucose tolerance observed in knock-out mice is due to increased total insulin secretion from a larger number of islet beta-cells. Homozygous males, 3 to 4 months of age, exhibit spatial learning and memory impairment as assessed in Morris water maze tests. Homozygotes (3 to 4 month old males) exhibit autistic-like behaviors including social approach and interaction behavior deficits, stereotype/repetitive behavior and abnormal vocalization. Knock-out mice display increased self-grooming and marble-burying behaviors. From postnatal day 2 through 12, homozygous pups emit more frequent, louder and longer isolation-induced ultrasonic vocalizations. Synaptic activity in hippocampal slices and spine density in CA1 pyramidal cell dendrites are increased in knock-out mice.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
24-month-old "4E-BP1/4E-BP2" double knockout mice (JAX Stock Numbers 031225 and 031507), on the congenic BALB/c background, exhibit higher muscle mass (due to reduced lean mass loss: 6% double KO mice and 20% in wildtype) and protein synthesis in muscle tissue, compared to wildtype controls.
A targeting vector containing a pTK-Neo cassette was used to disrupt exon 2. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into BALB/c blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were then backcrossed to BALB/cAnNCrl for seven generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize BALB/cByJ oocytes (Stock No. 001026).
|Allele Name||targeted mutation 1, Eric Klann|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||4E-BP2 KO|
|Gene Symbol and Name||Eif4ebp2, eukaryotic translation initiation factor 4E binding protein 2|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin resistance cassette replaced exon 2, disrupting amino acids 49-110. Western blot of hippocampal, cortical and cerebellar extracts confirmed the absence of protein in mutants.|
Heterozygous and homozygous mice are viable and fertile, but homozygotes exhibit autistic-like behaviors and spatial learning and memory impairment. Therefore, we maintain our live colony by breeding heterozygous mice to wildtype mice from the colony or to BALB/cByJ inbred mice (Stock No. 001026).
When using the 4E-BP2 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #031507 in your Materials and Methods section.
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