B6N.129-Gria1^tm2Rsp/J

Stock number: 019012
Product name: GluR-A^2lox
Research areas: Neurobiology Research, Research Tools, Sensorineural Research

Description

The GluA1^fl floxed exon 11 allele allows deletion of the sequences encoding the glutamate receptor transmembrane domain ion channel pore in cells/tissues expressing Cre recombinase. These mice are useful in applications related to the study of 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^fl floxed allele (also called GluR1^flox, GluR-A^2lox, or AQ-2lox allele) has loxP sites flanking exon 11. Homozygous mice are viable and fertile. When bred to mice that express Cre recombinase, the resulting offspring will have the glutamate receptor transmembrane domain ion channel pore deleted in cre-expressing tissues. These GluA1^fl mice may be useful in generating tissue-specific AMPA-type glutamate receptor deletions. Specific examples are described below.

When GluA1^fl mice are bred to a strain expressing Cre recombinase in germ-line or embryonic tissues, the resulting mice are useful in studying the pan deletion of glutamate receptor function. GluA1 knockout mice are also distributed from The Jackson Laboratory Repository as Stock No. 019011.

When GluA1^fl mice are bred to a strain with Cre recombinase in parvalbumin-expressing cells (see Stock Nos. 012358, 010777, 008069), the resulting mice allow studying interneurons and hippocampus function.

When GluA1^fl mice are bred to a strain with Cre recombinase in dopamine neurotransmitter transporter-expressing cells (see Stock Nos. 016583 or 006660), the resulting mice allow studying dopaminergic neurons.

When GluA1^fl mice are bred to a strain with Cre recombinase in Mnx1-expressing cells (HB9^cre; Stock No 006600), the resulting mice allow neurodevelopmental studies of homeobox genes, motor neurons, and a subpopulation of spinal cord interneurons.

When GluA1^fl mice are bred to a strain with tamoxifen-inducible Cre recombinase expression in glial high affinity glutamate transporter-expressing cells (see GLAST-CreER; Stock No 012586), the resulting mice allow neurodevelopmental studies of glia and neural progenitor cells.

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^fl genotype (exon 11 flanked by loxP sites and the neo selection cassette removed) were injected into recipient blastocysts. Chimeric mice were bred with C57BL/6 mice to establish the GluR-A^fl colony. The donating investigator reports that GluR-A^fl mice were subsequently backcrossed to C57BL/6NCrl mice for seven 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^tm2Rsp
Name: targeted mutation 2, Rolf Sprengel
MGI accession ID: MGI:3798452
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
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 floxed neo cassette was inserted 700 bp into exon 11 along with an additional loxP site inserted upstream of exon 10. This allele was used to generate Gria1^tm1Rsp by transfecting targeted ES cells with a cre-expressing vector (pMC-cre).