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

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F3N1F4p+N1 (09-NOV-05) Generation Definitions   Donating Investigator Dr. Gregg Homanics,   University of Pittsburgh

Description
The gamma subunit of the gamma aminobutyric acid type A receptor is essential for bestowing both normal single channel conductance and sensitivity to benzoidiazepines. Alternate RNA splicing produces two alternative forms of the gamma2 subunit from Gabrg2. The two forms, gamma2L and gamma2S are expressed in different brain regions. This strain is a knockout of the gamma2L form. Mice homozygous for this exon deletion are viable and superficially indistinguishable from wild type mice. Behaviorally, gamma2L knockout mice show increased levels of anxiety in the elevated plus maze relative to controls and also longer sleep time than control mice in response to midazolam and zolpidem.

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
The knockout was created through the replacement of a 0.6 kb XbaI fragment which includes the 24 bp exon 9 and associated splice signals with the bicistronic selectable marker gene (PGKneoNTRtkpA). The 129X1/SvJ x 129S1/Sv-derived ES (embryonic stem) cell line was used.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Gabrg2

016830	129X1.Cg-Gabrg2tm2Lusc/J
013209	B6.129(Cg)-Gabrg2tm1Spet/Frk
021197	STOCK Gabrg2tm1Wul/J

View Strains carrying other alleles of Gabrg2     (3 strains)

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, Childhood Absence, Susceptibility to, 2; ECA2   (GABRG2) Generalized Epilepsy with Febrile Seizures Plus, Type 3; GEFSP3   (GABRG2)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Gabrg2^tm1Geh/Gabrg2⁺

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

• reproductive system phenotype
• *normal* reproductive system phenotype
  • female mice exhibit normal fertility   (MGI Ref ID J:53823)
• • reduced male fertility
    • some mice exhibit reduced fertility while others are sterile   (MGI Ref ID J:53823)

Gabrg2^tm1Geh/Gabrg2^tm1Geh

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

• nervous system phenotype
• abnormal GABA-mediated receptor currents
  • GABA currents are more sensitive to inhibition by 5 uM zinc compared to in wild-type mice   (MGI Ref ID J:53823)
  • however, GABA currents are otherwise normal including sensitivity to midazolam and ethanol   (MGI Ref ID J:53823)
• homeostasis/metabolism phenotype
• abnormal xenobiotic pharmacokinetics
  • inhibition of flumazenil binding by midazolam, diazepam, and zolpidem is 10% to 14% greater than in wild-type mice while affinity towards betaCCM and Ro15-4513 is decreased 50% and 3-fold, respectively, compared to in wild-type mice   (MGI Ref ID J:102772)
• behavior/neurological phenotype
• *normal* behavior/neurological phenotype
  • mice exhibit normal ethanol-induced ataxia, anxiolysis, hyperlocomotor activity, tolerance and dependence   (MGI Ref ID J:53823)
  • mice exhibit normal balance on a rotarod   (MGI Ref ID J:53823)
• • enhanced behavioral response to xenobiotic
    • mice exhibit a 20% and 18% greater sleep time when exposed to midazolam and zolpidem, respectively, compared to similarly treated wild-type mice   (MGI Ref ID J:102772)
    • however, response to etomidate and pentobarbital is normal   (MGI Ref ID J:102772)

View Research Applications

Research Applications

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

Neurobiology Research
Receptor Defects
      GABA receptor

Gabrg2^tm1Geh related

Neurobiology Research
Receptor Defects

Research Tools
Neurobiology Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Gabrg2tm1Geh
Allele Name		targeted mutation 1, Gregg E Homanics
Allele Type		Targeted (knock-out)
Common Name(s)		Gabrgamma2Ltm1Geh;
Mutation Made By		Dr. Gregg Homanics,   University of Pittsburgh
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<+>
Gene Symbol and Name		Gabrg2, gamma-aminobutyric acid (GABA) A receptor, subunit gamma 2
Chromosome		11
Gene Common Name(s)		AI851231; BB128510; CAE2; ECA2; GABAA-R; GEFSP3; Gabrg-2; expressed sequence AI851231; expressed sequence BB128510; gamma2;
Molecular Note		A neomycin selection cassette replaced a genomic fragment containing exon 9. RT-PCR experiments demonstrated that this mutation resulted in the elimination of the expression of the long splice variant but not the short splice variant. Radioligand binding assays confirmed that no functional long variant was expressed from this allele. [MGI Ref ID J:53823]

Genotyping

Genotyping Information

Genotyping Protocols

Gabrg2^tm1Geh, Standard PCR
Gabrg2L^tm1Geh, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Homanics GE; Harrison NL; Quinlan JJ; Krasowski MD; Rick CE; de Blas AL ; Mehta AK ; Kist F ; Mihalek RM ; Aul JJ ; Firestone LL. 1999. Normal electrophysiological and behavioral responses to ethanol in mice lacking the long splice variant of the gamma2 subunit of the gamma-aminobutyrate type A receptor. Neuropharmacology 38(2):253-65. [PubMed: 10218866]  [MGI Ref ID J:53823]

Additional References

Gunther U; Benson J; Benke D; Fritschy JM; Reyes G; Knoflach F; Crestani F; Aguzzi A; Arigoni M; Lang Y; Bluethmann H; Mohler H; Luscher B. 1995. Benzodiazepine-insensitive mice generated by targeted disruption of the gamma 2 subunit gene of gamma-aminobutyric acid type A receptors. Proc Natl Acad Sci U S A 92(17):7749-53. [PubMed: 7644489]  [MGI Ref ID J:28662]

Gabrg2^tm1Geh related

Quinlan JJ; Firestone LL; Homanics GE. 2000. Mice lacking the long splice variant of the gamma 2 subunit of the GABA(A) receptor are more sensitive to benzodiazepines. Pharmacol Biochem Behav 66(2):371-4. [PubMed: 10880692]  [MGI Ref ID J:102772]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
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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