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. Species laboratory mouse Generation N5F8pN1 Generation Definitions   Donating Investigator Dr. 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 may relate to a genetic background differing from this JAX^® Mice strain.

Gabra2^tm1.1Geh/Gabra2^tm1.1Geh

        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 (knock-out)
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

Gabra2^tm1Geh, Standard PCR
Generic Neo Melt Curve Analysis,

Robotic MCA

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 & Husbandry	While 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

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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.

See Terms of Use tab for General Terms and Conditions

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.

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