|These mice carry S831A and S845A phosphorylation site mutations of GlurR1 (Gria1, glutamate receptor, ionotropic, AMPA1 (alpha 1)). Mutant mice exhibit deficits in synaptic plasticity and deterioration of learning/memory performance.|
Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Donating Investigator Richard L Huganir, Johns Hopkins University; HHMI
Mice that are homozygous for the S831A and S845A phosphorylation site mutations of GlurR1 are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Phosphorylation of the targeted amino acids is not detected by Western blot analysis of the brain isolated from homozygous animals. Mutant mice exhibit deficits in synaptic plasticity and deterioration of learning/memory performance.
A targeting vector containing a loxP site-flanked neomycin resistance cassette was inserted into intron 10 with alanine mutation in S831 and S845 sites. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1- Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice. After germline transmission, mice were bred to CMV-Cre transgenic mice to delete neomycin resistance cassette. The CMV-Cre transgene was bred out from the line and mutant mice carrying correct mutation were backcrossed to C57BL/6J more than 10 times.
Strains carrying other alleles of Gria1
024420 B6.129(Cg)-Gria1tm4Rlh/J 012614 B6.129-Gria1tm2Rlh/J 012612 B6.129-Gria1tm5Rlh/J 012613 B6.129-Gria1tm6Rlh/J 024418 B6.129S6-Gria1tm7Rlh/J 019011 B6N.129-Gria1tm1Rsp/J 019012 B6N.129-Gria1tm2Rsp/J 024422 C57BL/6-Gria1tm3Rlh/JView Strains carrying other alleles of Gria1 (8 strains)
View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.
Gria1tm1Rlh/Gria1tm1Rlhinvolves: 129S1/Sv * 129X1/SvJ * C57BL/6
- behavior/neurological phenotype
- abnormal associative learning
- mice fail to increase pokes of their nose into the prefered nose port upon a conditioned auditory cue while wild-type mice given the same training significantly increase the number of nose pokes by 5-fold (MGI Ref ID J:135196)
- the discrimination ratio between the conditioned and unconditioned noseport fails to be significantly different from chance (MGI Ref ID J:135196)
- the deficit in discriminating responding to the auditor cue is evident at the beginning of the test (i.e. does not result from differences in extinction rates) (MGI Ref ID J:135196)
- mice have no defects in normal food responses or overall locomotor activity (MGI Ref ID J:135196)
- abnormal long term spatial reference memory
- mutants exhibit a selective impairment in the retention of new learning at delays longer than a few hours, however learning is normal in the standard water maze task (MGI Ref ID J:82443)
- nervous system phenotype
- absent long term depression (MGI Ref ID J:82443)
- reduced long term potentiation
- LTP induced by theta burst stimulation is greatly reduced in adult, but not young, mutants (MGI Ref ID J:82443)
- LTP induced by a conventional 1 Hz protocol is absent in young (P21-P28) mutants (MGI Ref ID J:82443)
- LTP induced by pairing depolarizing current injection with low-frequency stimulation is severely reduced (MGI Ref ID J:82443)View Research ApplicationsResearch ApplicationsThis mouse can be used to support research in many areas including:
Behavioral and Learning Defects
glutamate receptor: ionotropic
|Allele Name||targeted mutation 1, Richard L Huganir|
|Mutation Made By||Richard Huganir, Johns Hopkins University; HHMI|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl<+>|
|ES Cell Line Name||R1|
|ES Cell Line Strain||(129X1/SvJ x 129S1/Sv)F1-Kitl<+>|
|Promoter||Gria1, glutamate receptor, ionotropic, AMPA1 (alpha 1), mouse, laboratory|
|Molecular Note||Alanine amino acid substitutions were introduced to phosphorylation sites serine 831 (S831A) and serine 845 (S845A) in exon 17 of the gene. A floxed neomycin resistance cassette was inserted upstream of exon 17 for positive selection. Mutant animals werecrossed to cre deleter strain Tg(CMV-cre)1Nagy to removed the floxed neo cassette, leaving behind the 2 amino acid substitutions. The targeted mutation was confirmed using immunoblot with phosphorylation site-specific antibodies. [MGI Ref ID J:82443]|
Lee HK; Takamiya K; Han JS; Man H; Kim CH; Rumbaugh G; Yu S; Ding L; He C; Petralia RS; Wenthold RJ; Gallagher M; Huganir RL. 2003. Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory. Cell 112(5):631-43. [PubMed: 12628184] [MGI Ref ID J:82443]
Crombag HS; Sutton JM; Takamiya K; Holland PC; Gallagher M; Huganir RL. 2008. A role for alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid GluR1 phosphorylation in the modulatory effects of appetitive reward cues on goal-directed behavior. Eur J Neurosci 27(12):3284-91. [PubMed: 18598267] [MGI Ref ID J:137440]
Crombag HS; Sutton JM; Takamiya K; Lee HK; Holland PC; Gallagher M; Huganir RL. 2008. A necessary role for GluR1 serine 831 phosphorylation in appetitive incentive learning. Behav Brain Res 191(2):178-83. [PubMed: 18455244] [MGI Ref ID J:135196]
Goel A; Xu LW; Snyder KP; Song L; Goenaga-Vazquez Y; Megill A; Takamiya K; Huganir RL; Lee HK. 2011. Phosphorylation of AMPA receptors is required for sensory deprivation-induced homeostatic synaptic plasticity. PLoS One 6(3):e18264. [PubMed: 21483826] [MGI Ref ID J:171435]
Hu H; Real E; Takamiya K; Kang MG; Ledoux J; Huganir RL; Malinow R. 2007. Emotion enhances learning via norepinephrine regulation of AMPA-receptor trafficking. Cell 131(1):160-73. [PubMed: 17923095] [MGI Ref ID J:141480]
Kim CH; Takamiya K; Petralia RS; Sattler R; Yu S; Zhou W; Kalb R; Wenthold R; Huganir R. 2005. Persistent hippocampal CA1 LTP in mice lacking the C-terminal PDZ ligand of GluR1. Nat Neurosci 8(8):985-7. [PubMed: 16007085] [MGI Ref ID J:101578]
Rakhade SN; Fitzgerald EF; Klein PM; Zhou C; Sun H; Hunganir RL; Jensen FE. 2012. Glutamate receptor 1 phosphorylation at serine 831 and 845 modulates seizure susceptibility and hippocampal hyperexcitability after early life seizures. J Neurosci 32(49):17800-12. [PubMed: 23223299] [MGI Ref ID J:193191]
Seol GH; Ziburkus J; Huang S; Song L; Kim IT; Takamiya K; Huganir RL; Lee HK; Kirkwood A. 2007. Neuromodulators control the polarity of spike-timing-dependent synaptic plasticity. Neuron 55(6):919-29. [PubMed: 17880895] [MGI Ref ID J:132105]
Svenningsson P; Bateup H; Qi H; Takamiya K; Huganir RL; Spedding M; Roth BL; McEwen BS; Greengard P. 2007. Involvement of AMPA receptor phosphorylation in antidepressant actions with special reference to tianeptine. Eur J Neurosci 26(12):3509-17. [PubMed: 18088278] [MGI Ref ID J:130859]
Animal Health ReportsProduction of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
|Pricing for USA, Canada and Mexico shipping destinations|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2525.00
At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
|Pricing for International shipping destinations|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $3283.00
Cryorecovery - Standard.
Progeny testing is not required.
For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.