Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Heterozygote x Heterozygote         (Female x Male)   27-DEC-12 Species laboratory mouse Generation N7pN1+ (01-MAR-13) Generation Definitions   Donating Investigator Rolf Sprengel,   Max Planck Institute for Medical Res

Description
The GluA1^fl floxed allele (also called GluR1^flox, GluR-A^2lox, or AQ-2lox allele) has loxP sites flanking exon 11. Homozygous mice are viable and fertile. When bred to mice that express Cre recombinase, the resulting offspring will have the glutamate receptor transmembrane domain ion channel pore deleted in cre-expressing tissues. These GluA1^fl mice may be useful in generating tissue-specific AMPA-type glutamate receptor deletions. Specific examples are described below.

When GluA1^fl mice are bred to a strain expressing Cre recombinase in germ-line or embryonic tissues, the resulting mice are useful in studying the pan deletion of glutamate receptor function. GluA1 knockout mice are also distributed from The Jackson Laboratory Repository as Stock No. 019011.

When GluA1^fl mice are bred to a strain with Cre recombinase in parvalbumin-expressing cells (see Stock Nos. 012358, 010777, 008069), the resulting mice allow studying interneurons and hippocampus function.

When GluA1^fl mice are bred to a strain with Cre recombinase in dopamine neurotransmitter transporter-expressing cells (see Stock Nos. 016583 or 006660), the resulting mice allow studying dopaminergic neurons.

When GluA1^fl mice are bred to a strain with Cre recombinase in Mnx1-expressing cells (HB9^cre; Stock No 006600), the resulting mice allow neurodevelopmental studies of homeobox genes, motor neurons, and a subpopulation of spinal cord interneurons.

When GluA1^fl mice are bred to a strain with tamoxifen-inducible Cre recombinase expression in glial high affinity glutamate transporter-expressing cells (see GLAST-CreER; Stock No 012586), the resulting mice allow neurodevelopmental studies of glia and neural progenitor cells.

Development
A targeting vector was designed to insert a loxP site upstream of exon 11, and a loxP-flanked neo cassette (from ploxpneo3) downstream of exon 11 of the glutamate receptor, ionotropic, AMPA1 [alpha 1] gene (Gria1; GluR-A, GluA1). This loxP::exon11::loxP::neo::loxP construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells with the GluR-A^neo allele (also called 3loxP allele) were then transiently transfected with a Cre recombinase-expressing plasmid. The resulting ES cells with the GluR-A^fl genotype (exon 11 flanked by loxP sites and the neo selection cassette removed) were injected into recipient blastocysts. Chimeric mice were bred with C57BL/6 mice to establish the GluR-A^fl colony. The donating investigator reports that GluR-A^fl mice were subsequently backcrossed to C57BL/6NCrl mice for seven generations prior to sending to The Jackson Laboratory Repository in 2012. Upon arrival, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation.

Control Information

	Control
	005304 C57BL/6NJ
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Gria1

008892	B6.129-Gria1tm1Rlh/J
012614	B6.129-Gria1tm2Rlh/J
012612	B6.129-Gria1tm5Rlh/J
012613	B6.129-Gria1tm6Rlh/J
019011	B6N.129-Gria1tm1Rsp/J

View Strains carrying other alleles of Gria1     (5 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Research Applications

Research Applications

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

Neurobiology Research
Behavioral and Learning Defects
      high anxiety
Channel and Transporter Defects
      calcium: glutamate receptor
Cortical Defects
Cre-lox System
      loxP-flanked Sequences
Neurotransmitter Receptor and Synaptic Vesicle Defects
Receptor Defects
      glutamate receptor: ionotropic

Research Tools
Cardiovascular Research
      Cre-lox System
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System
Diabetes and Obesity Research
      loxP
Genetics Research
      Mutagenesis and Transgenesis: Cre-lox System
Neurobiology Research
Reproductive Biology Research
      Cre-lox System

Sensorineural Research
Nociception

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Gria1tm2Rsp
Allele Name		targeted mutation 2, Rolf Sprengel
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		GRIA1fl; GluR-A2lox; GluR1flox;
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Gria1, glutamate receptor, ionotropic, AMPA1 (alpha 1)
Chromosome		11
Gene Common Name(s)		2900051M01Rik; AI853806; GLUH1; GLUR1; GLURA; Glr-1; Glr1; GluA1; GluR-A; Glur-1; Glur1; HBGR1; HIPA1; RIKEN cDNA 2900051M01 gene; expressed sequence AI853806; glutamate receptor 1; glutamate receptor 1 (alpha 1);
Molecular Note		A floxed neo cassette was inserted 700 bp into exon 11 along with an additional loxP site inserted upstream of exon 10. This allele was used to generate Gria1tm1Rsp by transfecting targeted ES cells with a cre-expressing vector (pMC-cre). [MGI Ref ID J:55695]

Genotyping

Genotyping Information

Genotyping Protocols

Gria1^tm2Rsp, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Emamian ES; Hall D; Birnbaum MJ; Karayiorgou M; Gogos JA. 2004. Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat Genet 36(2):131-7. [PubMed: 14745448]  [MGI Ref ID J:185487]

Engblom D; Bilbao A; Sanchis-Segura C; Dahan L; Perreau-Lenz S; Balland B; Parkitna JR; Lujan R; Halbout B; Mameli M; Parlato R; Sprengel R; Luscher C; Schutz G; Spanagel R. 2008. Glutamate receptors on dopamine neurons control the persistence of cocaine seeking. Neuron 59(3):497-508. [PubMed: 18701074]  [MGI Ref ID J:139693]

Fuchs EC; Zivkovic AR; Cunningham MO; Middleton S; Lebeau FE; Bannerman DM; Rozov A; Whittington MA; Traub RD; Rawlins JN; Monyer H. 2007. Recruitment of parvalbumin-positive interneurons determines hippocampal function and associated behavior. Neuron 53(4):591-604. [PubMed: 17296559]  [MGI Ref ID J:136763]

Zamanillo D; Sprengel R; Hvalby O; Jensen V; Burnashev N; Rozov A; Kaiser KM; Koster HJ; Borchardt T; Worley P; Lubke J; Frotscher M; Kelly PH; Sommer B; Andersen P; Seeburg PH; Sakmann B. 1999. Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning [see comments] Science 284(5421):1805-11. [PubMed: 10364547]  [MGI Ref ID J:55695]

Zhang L; Schessl J; Werner M; Bonnemann C; Xiong G; Mojsilovic-Petrovic J; Zhou W; Cohen A; Seeburg P; Misawa H; Jayaram A; Personius K; Hollmann M; Sprengel R; Kalb R. 2008. Role of GluR1 in activity-dependent motor system development. J Neurosci 28(40):9953-68. [PubMed: 18829953]  [MGI Ref ID J:141815]

Additional References

Gria1^tm2Rsp related

Gangadharan V; Wang R; Ulzhofer B; Luo C; Bardoni R; Bali KK; Agarwal N; Tegeder I; Hildebrandt U; Nagy GG; Todd AJ; Ghirri A; Haussler A; Sprengel R; Seeburg PH; MacDermott AB; Lewin GR; Kuner R. 2011. Peripheral calcium-permeable AMPA receptors regulate chronic inflammatory pain in mice. J Clin Invest 121(4):1608-23. [PubMed: 21383497]  [MGI Ref ID J:172020]

Lu W; Isozaki K; Roche KW; Nicoll RA. 2010. Synaptic targeting of AMPA receptors is regulated by a CaMKII site in the first intracellular loop of GluA1. Proc Natl Acad Sci U S A 107(51):22266-71. [PubMed: 21135237]  [MGI Ref ID J:167298]

Lu W; Shi Y; Jackson AC; Bjorgan K; During MJ; Sprengel R; Seeburg PH; Nicoll RA. 2009. Subunit composition of synaptic AMPA receptors revealed by a single-cell genetic approach. Neuron 62(2):254-68. [PubMed: 19409270]  [MGI Ref ID J:155070]

Racz A; Ponomarenko AA; Fuchs EC; Monyer H. 2009. Augmented hippocampal ripple oscillations in mice with reduced fast excitation onto parvalbumin-positive cells. J Neurosci 29(8):2563-8. [PubMed: 19244531]  [MGI Ref ID J:145942]

Saab AS; Neumeyer A; Jahn HM; Cupido A; Simek AA; Boele HJ; Scheller A; Le Meur K; Gotz M; Monyer H; Sprengel R; Rubio ME; Deitmer JW; De Zeeuw CI; Kirchhoff F. 2012. Bergmann glial AMPA receptors are required for fine motor coordination. Science 337(6095):749-53. [PubMed: 22767895]  [MGI Ref ID J:186487]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           MGL377

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Heterozygote x Heterozygote         (Female x Male)   27-DEC-12

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	005304 C57BL/6NJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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