Strain Name:

B6.129(FVB)-Gabra1tm1Geh/J

Stock Number:

004318

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Availability:

Cryopreserved - Ready for recovery

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Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6.129(FVB/N)-Gabra1    (Changed: 15-DEC-04 )
Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator IMR Colony,   The Jackson Laboratory

Description
These mice possess loxP sites flanking the second transmembrane domain of the gamma-aminobutyric acid (GABA) A receptor, subunit alpha 1 (Gabra1) gene. GABA is an inhibitory neurotransmitter in the nervous system which helps regulate neuronal excitability. Mice that are homozygous for this floxed Gabra1 allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants of Gabra1.

For example, when these mice are bred to B6.C-Tg(CMV-cre)1Cgn/J mice (Stock No. 006054) expressing cre in all tissues, the resulting double mutant mice exhibit sex-dependent decreased survival after P19, decreased body mass, EEG spike-wave discharges, and seizures. Heterozygotes display an intermediate decrease in body mass and survival.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Of note, several strains bearing gamma-aminobutyric acid (GABA-A) receptor mutations are available from this donating investigator (Dr. Gregg Homanics, University of Pittsburgh), including Gabra1 (Stock No. 004318), Gabra4 (Stock No. 006874), Gabra6 (Stock No. 002710), Gabrb3 (Stock No. 002711), Gabrd (Stock No. 003725), and Gabrg2 (Stock No. 003137).

Development
A targeting vector was constructed containing a selectable marker cassette (Neo/Tk) flanked by loxP sites. The loxP-flanked cassette was placed approximately 0.6 kb 5' of an exon encoding nucleotides 1307-1509 of the gamma-aminobutyric acid (GABA) A receptor, subunit alpha 1 (Gabra1) gene. A third loxP- site was placed approximately 0.8 kb 3' of the same exon. The construct was electroporated into 129X1/SvJ x 129S1/Sv-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a supercoiled cre expression plasmid for the purpose of removing the selectable marker cassette. ES cells that had successfully undergone Cre recombination and no longer retained the cassette but did retain the loxP-flanked exon (F) were injected in C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice and subsequently made homozygous (F/F). The homozygotes were bred to an actin-Cre general deleter on an FVB/N genetic background. Selected mice that were heterozygous for the flanked exon (F/+) and lacked the cre transgene were obtained and crossed to C57BL/6 animals.

Control Information

  Control
   None Available
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Gabra1
010948   B6;129-Gabra1tm4Geh/J
View Strains carrying other alleles of Gabra1     (1 strain)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Epilepsy, Juvenile Myoclonic, Susceptibility to, 5; EJM5   (GABRA1)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Gabra1tm1Geh/Gabra1tm1Geh

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N
  • normal phenotype
  • no abnormal phenotype detected
    • mice are equivalent to wild-type mice   (MGI Ref ID J:103381)
View Research Applications

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

Neurobiology Research
Cre-lox System
      loxP-flanked Sequences
Receptor Defects
      GABA receptor

Research Tools
Cre-lox System
      loxP-flanked Sequences

Gabra1tm1Geh related

Neurobiology Research
Neurotransmitter Receptor and Synaptic Vesicle Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Gabra1tm1Geh
Allele Name targeted mutation 1, Gregg E Homanics
Allele Type Targeted (Floxed/Frt)
Mutation Made ByDr. Gregg Homanics,   University of Pittsburgh
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Gabra1, gamma-aminobutyric acid (GABA) A receptor, subunit alpha 1
Chromosome 11
Gene Common Name(s) ECA4; EJM; EJM5; GABAA alpha 1; Gabra-1;
Molecular Note A loxP flanked neomycin and thymidine kinase cassette was inserted 5' to sequences corresponding to nucleotides 1307-1509, and a single loxP site was inserted 3' to these sequences. The loxP flanked neomycin selection cassette was removed in ES cells bytransient Cre recombinase expression prior to the production of chimeric mice, leaving a single loxP site in place of the cassette. [MGI Ref ID J:70505]

Genotyping

Genotyping Information

Genotyping Protocols

Gabra1tm1Geh, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Vicini S; Ferguson C; Prybylowski K; Kralic J; Morrow AL; Homanics GE. 2001. GABA(A) receptor alpha1 subunit deletion prevents developmental changes of inhibitory synaptic currents in cerebellar neurons. J Neurosci 21(9):3009-16. [PubMed: 11312285]  [MGI Ref ID J:70505]

Additional References

Gabra1tm1Geh related

Briatore F; Patrizi A; Viltono L; Sassoe-Pognetto M; Wulff P. 2010. Quantitative organization of GABAergic synapses in the molecular layer of the mouse cerebellar cortex. PLoS One 5(8):e12119. [PubMed: 20711348]  [MGI Ref ID J:163757]

Gafford GM; Guo JD; Flandreau EI; Hazra R; Rainnie DG; Ressler KJ. 2012. Cell-type specific deletion of GABA(A)alpha1 in corticotropin-releasing factor-containing neurons enhances anxiety and disrupts fear extinction. Proc Natl Acad Sci U S A 109(40):16330-5. [PubMed: 22992651]  [MGI Ref ID J:190101]

Goldstein PA; Elsen FP; Ying SW; Ferguson C; Homanics GE; Harrison NL. 2002. Prolongation of hippocampal miniature inhibitory postsynaptic currents in mice lacking the GABA(A) receptor alpha1 subunit. J Neurophysiol 88(6):3208-17. [PubMed: 12466441]  [MGI Ref ID J:103381]

Heldt SA; Ressler KJ. 2010. Amygdala-specific reduction of alpha1-GABAA receptors disrupts the anticonvulsant, locomotor, and sedative, but not anxiolytic, effects of benzodiazepines in mice. J Neurosci 30(21):7139-51. [PubMed: 20505082]  [MGI Ref ID J:165047]

Wiltgen BJ; Godsil BP; Peng Z; Saab F; June HL; Linn ML; Cook JM; Houser CR; O'Dell TJ; Homanics GE; Fanselow MS. 2009. The alpha1 subunit of the GABA(A) receptor modulates fear learning and plasticity in the lateral amygdala. Front Behav Neurosci 3:37. [PubMed: 19876409]  [MGI Ref ID J:180420]

Zeller A; Crestani F; Camenisch I; Iwasato T; Itohara S; Fritschy JM; Rudolph U. 2008. Cortical glutamatergic neurons mediate the motor sedative action of diazepam. Mol Pharmacol 73(2):282-91. [PubMed: 17965197]  [MGI Ref ID J:148144]

Zhou C; Huang Z; Ding L; Deel ME; Arain FM; Murray CR; Patel RS; Flanagan CD; Gallagher MJ. 2013. Altered cortical GABAA receptor composition, physiology, and endocytosis in a mouse model of a human genetic absence epilepsy syndrome. J Biol Chem 288(29):21458-72. [PubMed: 23744069]  [MGI Ref ID J:201781]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryThis strain originated on a B6;129 background, was crossed to a pure FVB/N mouse once (a Cre strain) and then crossed to C57BL/6 animals for at least 6 generations (2/02).Coat color expected from breeding:Black

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2450.00
Animals Provided

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.

Embryos

Price (US dollars $)
Frozen Embryo $1600.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • 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 11 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 View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3185.00
Animals Provided

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.

Embryos

Price (US dollars $)
Frozen Embryo $2080.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • 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 11 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).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   None Available
 
  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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"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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