C57BL/6J-Grm2^em1Geh/J

Stock number: 038874
Product name: Grm2^f
Research areas: Neurobiology Research, Research Tools

Description

Grm2^f conditional knock in mice have loxP sites flanking exon 3 of the Grm2 (glutamate receptor, metabotropic 2) gene. These mice may be useful for studying drug and alcohol consumption.

Detailed description

Grm2 (glutamate receptor, metabotropic 2) encodes a member of the family of G protein-coupled receptors and is expressed only in the brain, specifically on the glutamatergic presynaptic terminal. GRM2 functions to modulate glutamate transmission in the dorsolateral striatum, nucleus accumbens, and amygdala. Loss of Grm2 is associated with increased levels of drug and alcohol consumption.

Grm2^f knock in mice have loxP sites flanking exon 3. Mice that are homozygous for this floxed allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 3 deleted in the cre-expressing tissues. Loss of exon 3 results in a null allele.

When combined with mice carrying a Cre recombinase with expression in telencephalon-lineage neurons (B6.129S2-Emx1^tm1(cre)Krj/J, Stock No. 005628), male double mutant progeny exhibit some impairment in reversal learning using a palatable food reinforcer and a reduction in response vigor in males trained under a high effort random ration reinforcement schedule.

Development

CRISPR/cas9 endonuclease-mediated genome editing was used to insert loxP sites in introns 2 and 3 of the Grm2 (glutamate receptor, metabotropic 2) gene on chromosome 9. Single guide RNAs, cas9 endonuclease and loxP targeting oligonucleotides were electroporated into C57BL/6J-derived zygotes. Grm2 transcript Grm2-201 (ENSMUST00000023959.13) was used as reference for the exon number and guide sequences. Embryos were transferred to pseudopregnant females, and correctly targeted pups were bred to C57BL/6J mice for germline transmission and then bred to C57BL/6J for an additional generation. Southern blot and DNA sequencing confirmed the mutation. Deletion of exon 3 (specifically, 838 bp) is predicted to cause a frameshift mutation. The colony was maintained on the C57BL/6J background. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Grm2^em1Geh
Name: endonuclease-mediated mutation 1, Gregg Homanics
MGI accession ID: MGI:7530802
Generation method: Endonuclease-mediated
Attributes: Conditional ready (e.g. floxed)
Synonyms: Grm2^f
Marker symbol: Grm2
Marker name: glutamate receptor, metabotropic 2
Marker synonyms: 4930441L02Rik; GLUR2; Gprc1b; mGlu2; MGLUR2
Chromosome: 9
Strain of origin: C57BL/6J
Molecular note: CRISPR/cas9 endonuclease-mediated genome editing is used to insert loxP sites in introns 2 and 3. Grm2 transcript Grm2-201 (ENSMUST00000023959.13) was used as reference for the exon number and guide sequences.