B6.129S6(Cg)-Gria2^tm3.1Rlh/J

Stock number: 037072
Product name: GluA2 Y876F
Research areas: Neurobiology Research, Research Tools

Description

These mice possess a Y876F mutation in the GluA2 gene, a phosphorylation site which plays an important role in synaptic plasticity. These mice may have applications in studies related to synapse-specific Hebbian plasticity and network-level homeostatic plasticity.

Detailed description

These mice possess a Y876F mutation in the glutamate receptor, ionotropic, AMPA2 (alpha 2) (GluA2) gene, a phosphorylation site which plays an important role in synaptic plasticity. GluA2 encodes a subunit of an AMPA glutamate receptor that function as a ligand-activated cation channel. AMPA receptors mediate fast excitatory synaptic transmission.

These mice have ablated in vivo and in vitro homeostatic upscaling. Lack of GluA2 pY876 does not affect the number of excitatory synapses.

Homozygous mice are viable and fertile. The donating investigator reports that homozygotes females can occasionally experience dystocia, and the homozygotes males can tend to be aggressive as they age.

Development

A targeting construct was designed to insert an adenosine to thymidine point mutation, resulting in a tyrosine to phenylalanine substitution at position 876 (Y876F), in the glutamate receptor, ionotropic, AMPA2 (alpha 2) (GluA2) gene. A loxP-flanked neomycin (neo) resistance cassette, in opposite orientation to the gene, was placed upstream of the mutated exon. This targeting construct was electroporated into 129S6/SvEvTac-derived MC1 embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. The resulting GluA2 Y876F knock-in chimeric mice were bred with CMV-Cre mice on an unknown background to remove the floxed neo cassette. Resulting offspring were backcrossed to C57BL/6J mice for 12 generations. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Gria2^tm3.1Rlh
Name: targeted mutation 3.1, Richard Huganir
MGI accession ID: MGI:6864289
Generation method: Targeted
Attributes: Not Specified
Synonyms: GluA2 Y876F
Marker symbol: Gria2
Marker name: glutamate receptor, ionotropic, AMPA2 (alpha 2)
Marker synonyms: GluA2; GLUR2; Glur-2; GLURB; GluR-B; GluR-K2; HBGR2; NEDLIB
Chromosome: 3
Strain of origin: 129S2/SvPas
Molecular note: The targeting construct is designed to insert an adenosine to thymidine point mutation, resulting in a tyrosine to phenylalanine substitution at position 876 (Y876F). A loxP-flanked neomycin (neo) resistance cassette, in opposite orientation to the gene, is placed upstream of the mutated exon. Germ line, cre mediated recombination removed the neo cassette.