B6.129S6-Gria1^tm7Rlh/J

Stock number: 024418
Research areas: Neurobiology Research

Description

These mice carry S831D and S845D amino acid substitutions in the mouse Gria1 gene that are phosphomimetic (mimic a phosphorylated protein). Phosphorylation at these amino acids is sufficient to lower the threshold for LTP induction, increasing the probability of synaptic plasticity.

Detailed description

Phosphorylation of Gria1 (glutamate receptor, ionotropic, AMPA1 (alpha 1); also known as GluA1) has been proposed to regulate receptor trafficking and synaptic transmission and plasticity.

These mice carry S831D and S845D amino acid substitutions in the mouse Gria1 gene that are phosphomimetic (mimic a phosphorylated protein). Mice show normal total and surface expression and subcellular localization of GLUA1 as well as intact basal synaptic transmission. Unlike wildtype animals, mutant mice show long-term potentiation (LTP) induced with a weak 10-Hz stimulation. Evidence indicates that phosphorylation of GLUA1 at S831 and S845 is sufficient to lower the threshold for LTP induction, increasing the probability of synaptic plasticity.

Development

S831D (TCC->GAT) and S845D (AGC->GAC) serine to aspartate mutations were introduced to GluA1 (Gria1) cDNA using QuikChange site-directed mutagenesis (Stratagene). The mutations were introduced to 129S6/SvEvTac-derived MC1 embryonic stem (ES) cells by homologous recombination. This strain was backcrossed to C57BL/6 for 10 generations by the donating laboratory.

Allele

Symbol: Gria1^tm7Rlh
Name: targeted mutation 7, Richard L Huganir
MGI accession ID: MGI:5562310
Generation method: Targeted
Marker symbol: Gria1
Marker name: glutamate receptor, ionotropic, AMPA1 (alpha 1)
Chromosome: 11
Strain of origin: 129S6/SvEvTac
Molecular note: S831D (TCC to GAT) and S845D (AGC to GAC) serine to aspartate mutations were introduced to GluA1 (Gria1) cDNA using QuikChange site-directed mutagenesis (Stratagene).