Grin2aΔPKC Grin2a mutant mice have amino acid substitutions that result in nonphosphorylatable PKC sites. These mice may be suitable for use in studies related to synaptic plasticity, memory and learning.
John P Leonard, University of Illinois at Chicago
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Not Applicable) | Grin2a | glutamate receptor, ionotropic, NMDA2A (epsilon 1) |
The targeted Grin2a gene encodes the GluN2A NMDA receptor subunit. Mutations in this gene have been associated with Focal Epilepsy and Speech Disorder with or without Mental Retardation and Landau-Kleffner Syndrome. These Grin2aΔPKC mice carry the unphosphorylatable amino acid substitutions S1991A, Y1292F, S1312A and Y1472F (encoded by exon 12), which are sites of Protein kinase C phosphorylation.
Mutant homozygous mice exhibit decreased anxiety-related behaviors, as assessed in open field test, light dark emergence test, and elevated plus maze. Slight spatial working memory impairment is also observed in homozygotes (reduced spontaneous Y maze alternation and reduced delayed T maze alternation). Mice that are homozygous for the targeted mutation are viable and fertile.
Gene product (mRNA or protein) expression levels in mutant mice are similar to that observed in wildtype controls, as determined by Northern or Western blot analysis.
A targeting vector containing mutations that result in amino acid substitutions S1991A, Y1292F, S1312A and Y1472F, and a loxP site flanked NEO cassette was used to disrupt exon 12. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.
The resulting chimeric animals were bred to C57BL/6 mice to achieve germline transmission.
The mice were then crossed to Ella-cre mice on the C57BL/6 and FVB genetic background to remove the floxed NEO cassette. Mice that no longer carried the NEO cassette were bred to C57BL/6J for 5 generations.
Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
Allele Name | targeted mutation 1.1, John P Leonard |
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Allele Type | Targeted (Not Applicable) |
Allele Synonym(s) | deltaPKC; Grin2adeltaPKC |
Gene Symbol and Name | Grin2a, glutamate receptor, ionotropic, NMDA2A (epsilon 1) |
Gene Synonym(s) | |
Strain of Origin | 129S4/SvJae |
Chromosome | 16 |
Molecular Note | A targeting vector containing mutations that result in amino acid substitutions S1991A, Y1292F, S1312A and Y1472F, and a loxP site flanked NEO cassette was used to disrupt exon 12. Cre-mediated recombination removed the floxed neo cassette. |
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Grin2aΔPKC mouse strain in a publication, please cite the originating article(s) and include JAX stock #027998 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or wildtype for Grin2a<tm1.1Jpleo> |
Frozen Mouse Embryo | B6.129S4(FVB)-Grin2a<tm1.1Jpleo>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129S4(FVB)-Grin2a<tm1.1Jpleo>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129S4(FVB)-Grin2a<tm1.1Jpleo>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.129S4(FVB)-Grin2a<tm1.1Jpleo>/J Frozen Embryo | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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