Strain Name:

B6.129-Gabra2tm1.1Geh/J

Stock Number:

012942

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Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use
This HA/HA mutant mouse strain may be useful in studies of the effects of alcohol and anesthesia, behavior, learning and memory.

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-Gabra2tm1Geh/J    (Changed: 01-JUN-11 )
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
GenerationN5F8pN1
Generation Definitions
 
Donating InvestigatorDr. Gregg Homanics,   University of Pittsburgh

Description
These mutant mice carry substitutions of serine to histidine at amino acid position 270 and leucine to alanine at amino acid position 277 of exon 9. The point mutations confer alcohol and anesthesia insensitivity, while retaining near-normal GABA sensitivity. Approximately half of the homozygous mutant mice (from heterozygous crosses) die between birth and weaning. Homozygotes that survive to adulthood are fertile, normal in size and do not display any gross physical abnormalities. Mutant gene product (mRNA) is detected by RT-PCR analysis of whole brain total RNA. The alpha2 subunit protein levels did not differ between mice homozygous for the mutation and wildtype mice in the cortex and hippocampus. Homozygotes exhibit enhanced fear conditioning, reduced sensitivity to anesthesia (isoflurane), increased alcohol consumption without typical conditioned taste aversion, reduced ethanol induced stimulation of motor activity, and recover more slowly from ethanol?induced hypnosis. Dentate gyrus granule neurons exhibit decreased decay time constant (miniature inhibitory postsynaptic current) and in response to isoflurane, prolongation of the decay phase is decreased. Male mutants showed increased avoidance of bitter taste (quinine). Homozygotes display some enhanced learning and memory.

Development
The targeting vector was designed (by site-directed mutagenesis) to substitute a serine to histidine at amino acid position 270 and leucine to alanine at amino acid position 277 of exon 9. An FRT-flanked PGKneo cassette was inserted downstream of exon 9. 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 C57BL/6J blastocysts. The resulting male chimeric animals were crossed to C57BL/6J female mice. Heterozygous mice were crossed to B6.Cg-Tg(ACTFLPe)9205Dym/J (actin-FLPe) to remove the neo cassette and leave a single FRT site downstream of exon 9. The mice were backcrossed to C57BL/6J for 5 generations and the Flpe transgene was subsequently bred out. Upon arrival at The Jackson Laboratory the mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

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.
Alcohol Dependence   (GABRA2)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Gabra2tm1.1Geh/Gabra2tm1.1Geh

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
  • mortality/aging
  • partial postnatal lethality
    • despite normal representation prior to birth, mice are under-represented at weaning   (MGI Ref ID J:171967)
  • behavior/neurological phenotype
  • enhanced behavioral response to anesthetic
    • isoflurane-treated mice exhibit increased sedation, immobility, and recovery time compared with similarly treated wild-type mice   (MGI Ref ID J:171967)
    • however, response to halothane is normal and additional backcrossing to C57BL/6 restores recovery from isoflurane   (MGI Ref ID J:171967)
  • enhanced contextual conditioning behavior   (MGI Ref ID J:171967)
  • enhanced cued conditioning behavior   (MGI Ref ID J:171967)
  • nervous system phenotype
  • abnormal miniature inhibitory postsynaptic currents
    • the average decay time constant of miniature inhibitory postsynpatic currents in hippocampal dentate granule cells is reduced compared to in wild-type cells   (MGI Ref ID J:171967)
    • isoflurane treatment induced a reduced percentage change in decay time constant in hippocampal dentate granule cells compared to in wild-type cells   (MGI Ref ID J:171967)
View Research Applications

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

Cell Biology Research
Channel and Transporter Defects
      chloride
      chloride: GABAA receptor

Neurobiology Research
Channel and Transporter Defects
      chloride
      chloride: GABAA receptor
Receptor Defects
      GABA receptor

Research Tools
Neurobiology Research
Sensorineural Research

Sensorineural Research
Taste Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Gabra2tm1.1Geh
Allele Name targeted mutation 1.1, Gregg E Homanics
Allele Type Targeted (Null/Knockout)
Common Name(s) Gabra2HA;
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Gabra2, gamma-aminobutyric acid (GABA) A receptor, subunit alpha 2
Chromosome 5
Gene Common Name(s) C630048P16Rik; Gabra-2; RIKEN cDNA C630048P16 gene;
Molecular Note The targeting vector was designed (by site-directed mutagenesis) to substitute a serine to histidine at amino acid position 270 and leucine to alanine at amino acid position 277 of exon 9. An FRT-flanked PGKneo cassette was inserted downstream of exon 9.Flp-mediated recombination removed the neo cassette and left a single FRT site downstream of exon 9. [MGI Ref ID J:171967]

Genotyping

Genotyping Information

Genotyping Protocols

Gabra2tm1Geh, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Werner DF; Swihart A; Rau V; Jia F; Borghese CM; McCracken ML; Iyer S; Fanselow MS; Oh I; Sonner JM; Eger EI 2nd; Harrison NL; Harris RA; Homanics GE. 2011. Inhaled anesthetic responses of recombinant receptors and knockin mice harboring alpha2(S270H/L277A) GABA(A) receptor subunits that are resistant to isoflurane. J Pharmacol Exp Ther 336(1):134-44. [PubMed: 20807777]  [MGI Ref ID J:171967]

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 & HusbandryWhile maintaining a live colony, these mice can be bred as heterozygotes. Approximately half of homozygotes die between birth and weaning, survivors are fertile, normal in size and do not display any gross physical abnormalities.

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* $2140.00
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.

Standard Supply

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

Supply Notes

  • 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 willfulfill 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 View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
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.

Standard Supply

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

Supply Notes

  • 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 willfulfill 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).

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
   Wild-type from the colony
   000664 C57BL/6J
 
  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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