The GluA1fl 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, as well as neuropsychiatric disorders such as schizophrenia and depression/mania.
Rolf Sprengel, Max Planck Institute for Medical Res
The GluA1fl floxed allele (also called GluR1flox, GluR-A2lox, 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 GluA1fl mice may be useful in generating tissue-specific AMPA-type glutamate receptor deletions. Specific examples are described below.
When GluA1fl 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 GluA1fl 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 GluA1fl 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 GluA1fl mice are bred to a strain with Cre recombinase in Mnx1-expressing cells (HB9cre; Stock No 006600), the resulting mice allow neurodevelopmental studies of homeobox genes, motor neurons, and a subpopulation of spinal cord interneurons.
When GluA1fl 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.
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-Aneo allele (also called 3loxP allele) were then transiently transfected with a Cre recombinase-expressing plasmid. The resulting ES cells with the GluR-Afl 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-Afl colony. The donating investigator reports that GluR-Afl 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 Name||targeted mutation 2, Rolf Sprengel|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||GluR1flox; GluR-A2lox; GRIA1fl|
|Gene Symbol and Name||Gria1, glutamate receptor, ionotropic, AMPA1 (alpha 1)|
|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 Gria1tm1Rsp by transfecting targeted ES cells with a cre-expressing vector (pMC-cre).|
When maintaining a live colony, homozygous mice may be bred together.
When using the GluR-A2lox mouse strain in a publication, please cite the originating article(s) and include JAX stock #019012 in your Materials and Methods section.