B6.129-Gria1^tm1Rlh/J

Stock number: 008892
Research areas: Neurobiology Research

Description

These mice carry S831A and S845A phosphorylation site mutations of GlurR1 (Gria1, glutamate receptor, ionotropic, AMPA1 (alpha 1)). Mutant mice exhibit deficits in synaptic plasticity and deterioration of learning/memory performance.

Detailed description

Mice that are homozygous for the S831A and S845A phosphorylation site mutations of GlurR1 are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Phosphorylation of the targeted amino acids is not detected by Western blot analysis of the brain isolated from homozygous animals. Mutant mice exhibit deficits in synaptic plasticity and deterioration of learning/memory performance.

Development

A targeting vector containing a loxP site-flanked neomycin resistance cassette was inserted into intron 10 with alanine mutation in S831 and S845 sites. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice. After germline transmission, mice were bred to CMV-Cre transgenic mice to delete neomycin resistance cassette. The CMV-Cre transgene was bred out from the line and mutant mice carrying correct mutation were backcrossed to C57BL/6J more than 10 times.

Allele

Symbol: Gria1^tm1Rlh
Name: targeted mutation 1, Richard L Huganir
MGI accession ID: MGI:2653986
Generation method: Targeted
Attributes: Not Specified
Marker symbol: Gria1
Marker name: glutamate receptor, ionotropic, AMPA1 (alpha 1)
Chromosome: 11
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: Alanine amino acid substitutions were introduced to phosphorylation sites serine 831 (S831A) and serine 845 (S845A) in exon 17 of the gene. A floxed neomycin resistance cassette was inserted upstream of exon 17 for positive selection. Mutant animals were crossed to cre deleter strain Tg(CMV-cre)1Nagy to removed the floxed neo cassette, leaving behind the 2 amino acid substitutions. The targeted mutation was confirmed using immunoblot with phosphorylation site-specific antibodies.