B6N.129-Gria1^tm1Rsp/J

Stock number: 019011
Product name: GluA1 KO , GluA1- , GluR1- , GluR-A- , GluRA-
Research areas: Neurobiology Research, Research Tools, Sensorineural Research

Description

GluA1 knockout mice exhibit behavioral, social, and cognitive deficits. They may have applications in studies related to behavioral, social and cognitive abnormalities, hippocampal synaptic transmission/plasticity, nociception and short and long term memory, as well as neuropsychiatric disorders such as schizophrenia and depression/mania.

Detailed description

The GluA1 knockout allele (also called GluA1^-, GluR-A^-, or A1-lox) has a deletion of the sequences necessary in formation of the glutamate receptor transmembrane domain ion channel pore (exon 11). No GluA1 protein expression is detected from the targeted allele. Homozygous mice are viable and fertile, with behavioral, social, and cognitive deficits. Specifically, homozygotes have profound impairment of several different spatial working memory tasks and selective impairment on short-term recognition memory tasks. Homozygotes show no alterations on spatial reference memory tasks or long-term memory tasks. GluA1^-/- mice also have novelty- and stress-induced hyperactivity, and increased anxiety-related responses. Hippocampal CA1 pyramidal neurons from homozygous mice have strongly reduced extrasynaptic AMPA currents and do not show the dendritic distance-dependent scaling of excitatory synaptic strengths seen in wildtype neurons.

Development

A targeting vector was designed to insert a loxP site upstream of exon 11, and a loxP-flanked neo cassette (from ploxpneo3) downstream of exon 11 of the glutamate receptor, ionotropic, AMPA1 [alpha 1] gene (Gria1; GluR-A, GluA1). This loxP::exon11::loxP::neo::loxP construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells with the GluR-A^neo allele (also called 3loxP allele) were then transiently transfected with a Cre recombinase-expressing plasmid. The resulting ES cells with the GluR-A^- genotype (both exon 11 and neo selection cassette removed; leaving a single loxP site remaining) were injected into recipient blastocysts. Chimeric mice were bred with C57BL/6 mice to establish the mutant colony. The donating investigator reports that GluR-A^- mice were subsequently backcrossed to C57BL/6NCrl mice for ten generations prior to sending to The Jackson Laboratory Repository in 2012. Upon arrival, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation.

Allele

Symbol: Gria1^tm1Rsp
Name: targeted mutation 1, Rolf Sprengel
MGI accession ID: MGI:2178057
Generation method: Targeted
Attributes: Null/Knockout
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: A single loxP site was inserted into intron 10 and a loxP flanked neomycin selection cassette was inserted into exon 11. The loxP-flanked sequences were deleted in ES cells by transient Cre expression prior to the production of chimeric mice. The final heritable allele contains a single loxP site replacing exon 11 and flanking intronic sequences. Immunohistochemistry experiments confirmed that no detectable protein is expressed from this allele.
General note: Phenotypic Similarity to Human Syndrome: Schizoaffective Disorder (J:167264).