B6(Cg)-Grin1^{tm1c(EUCOMM)Wtsi}/ZwzJ

Stock number: 018825
Research areas: Neurobiology Research, Research Tools

Description

These Grin1^2lox mice possess loxP sites flanking exon 6 of the glutamate receptor, ionotropic, NMDA1 (zeta 1), Grin1, gene and have applications in studies related to the involvement of NMDA receptors in synaptogenesis, synaptic plasticity and neurological disorders.

Detailed description

Grin1 encodes an essential subunit of the NMDA (N-methyl-D-aspartate) receptor, a glutamate receptor and ligand-gated channel that has a critical role in CNS excitatory synaptic transmission and plasticity. These mice possess loxP sites on either side of exon 6 of the targeted gene. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 4 deleted in the cre-expressing tissues.

When bred to a strain with Cre recombinase expression in neurons of the cortex and thalamus in postnatal day 2 aged mice, this mutant mouse strain may be useful in studies of synaptic refinement.

Development

A targeting vector containing a human beta-actin promoter-driven selection cassette consisting of a FRT site, lacZ sequence, the first loxP site, human beta-actin promoter driving the neomycin resistance gene, SV40 polyA, FRT site and a second loxP site was inserted downstream of exon 6 of the targeted gene, and another loxP site was inserted upstream of exon 6. This construct was electroporated into C57BL/6N-A^tm1Brd derived JM8A3.N1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into B6(Cg)-Tyr^c-2J/J blastocysts (derived from Stock No. 000058). The resulting chimeric animals were bred to B6(Cg)-Tyr^c-2J/J to achieve germline transmission. Offspring carrying the targeted mutation were crossed to mice with germline FLP recombinase expression, B6.Cg-Tg(ACTFLPe)9205Dym/J, (Stock No. 005703), to remove the NEO selection cassette. Mice that retained the loxP site-flanked exon 6, Grin1^2lox, were then bred to C57BL/6J mice for one or two generations to remove the FLP recombinase transgene. Heterozygotes were crossed to generate homozygotes. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6NJ (Stock No. 005304) at least once to establish the colony.

Allele

Symbol: Grin1^{tm1c(EUCOMM)Wtsi}
Name: targeted mutation 1c, Wellcome Trust Sanger Institute
MGI accession ID: MGI:5431094
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Marker symbol: Grin1
Marker name: glutamate receptor, ionotropic, NMDA1 (zeta 1)
Chromosome: 2
Strain of origin: C57BL/6N-A^tm1Brd
Molecular note: A targeting vector containing a human beta-actin promoter-driven selection cassette consisting of a FRT site, lacZ sequence, the first loxP site, human beta-actin promoter driving the neomycin resistance gene, SV40 polyA, FRT site and a second loxP site was inserted downstream of exon 6 of the targeted gene, and another loxP site was inserted upstream of exon 6. Flp-mediated recombination removed the lacZ and neo cassette and left exon 6 floxed.
General note: Cell line EPD0469_5_G09 and EPD0469_5_C11 were successfully used to make chimeric mice. Germline transmission was accomplished. J:155845 J:193625