Overview

Also Known As:Grin2aΔPKC

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.

Donating Investigator

John P Leonard, University of Illinois at Chicago

Genetic overview

Genetic Background	Generation

Grin2a^tm1.1Jpleo

Allele Type	Gene Symbol	Gene Name
Targeted (Not Applicable)	Grin2a	glutamate receptor, ionotropic, NMDA2A (epsilon 1)

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Research Applications

Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

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.

Development

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.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Balu D; Larson JR; Schmidt JV; Wirtshafter D; Yevtodiyenko A; Leonard JP. 2016. Behavioral and physiological characterization of PKC-dependent phosphorylation in the Grin2aPKC mouse. Brain Res 1646:315-26PubMed: 27317637 MGI: J:235504

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Genetics

Grin2a^tm1.1Jpleo

Allele Symbol: Grin2a^tm1.1Jpleo

Allele Name	targeted mutation 1.1, John P Leonard
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.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Neurobiology Research
- Behavioral and Learning Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Grin2a^tm1.1Jpleo/Grin2a^tm1.1Jpleo
involves: 129S4/SvJae * C57BL/6 * FVB/N

behavior/neurological phenotype

decreased exploration in new environment
- alternation rate is decreased in Y maze and delayed T arm maze as compared to controls
- however, there is no significant difference in general activity levels

decreased anxiety-related response
- increased time in center of open field
- mice exhibit reduced anxiety levels as measured by open field, light/dark box, and elevated plus maze
- more time in the lit compartment of the light-dark box
- increased time in open arms of elevated plus maze

abnormal spatial working memory
- alternation rate is decreased in Y maze and delayed T arm maze as compared to controls
- however, there is no significant difference in general activity levels

mammalian phenotype

nervous system phenotype
- Normal - measurement of brain electrophysiology, including LTP, indicated no significant genotype differences

References

Balu D; Larson JR; Schmidt JV; Wirtshafter D; Yevtodiyenko A; Leonard JP. 2016. Behavioral and physiological characterization of PKC-dependent phosphorylation in the Grin2aPKC mouse. Brain Res 1646:315-26PubMed: 27317637 MGI: J:235504

Additional - Grin2a^tm1.1Jpleo related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Grin2a-Alternate 1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
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.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous or wildtype for Grin2a<tm1.1Jpleo>

Related Products and Services

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

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Grin2aΔPKC

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Grin2atm1.1Jpleo

Allele Symbol: Grin2atm1.1Jpleo

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Grin2atm1.1Jpleo/Grin2atm1.1Jpleoinvolves: 129S4/SvJae * C57BL/6 * FVB/N

behavior/neurological phenotype

mammalian phenotype

References

Additional - Grin2atm1.1Jpleo related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Grin2a^tm1.1Jpleo

Allele Symbol: Grin2a^tm1.1Jpleo

Genotype: Grin2a^tm1.1Jpleo/Grin2a^tm1.1Jpleo
involves: 129S4/SvJae * C57BL/6 * FVB/N

Additional - Grin2a^tm1.1Jpleo related