Overview

Compared to wild-type mice, these Gabra6 knock-out mice exhibit an absence of a dramatic alteration in behavioral response to neuroactive compounds.

Donating Investigator

Gregg E Homanics, University of Pittsburgh

Genetic overview

Genetic Background	Generation

Gabra6^tm1Geh

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Gabra6	gamma-aminobutyric acid (GABA) A receptor, subunit alpha 6

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Research Applications

Neurobiology Research
Cell Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the Gabra6^tm1Geh mutation are viable and fertile with no gross abnormalities. There were no differences detected in behavioral response to ethanol comparing homozygotes to wildtypes from the two background strains, C57BL/6 and 129/SvJ. These findings suggest that the alpha6 subunit of the gamma-aminobutyric acid type A receptor exerts little if any influence on acute functional tolerance, withdrawal hyperexcitability, or protracted tolerance. The only defects discovered thus far are pharmacologic.

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

This strain was developed in the laboratory of Dr. Gregg Homanics at the University of Pittsburgh. The vector containing Pgk-neo was inserted by homologous recombination into exon 8 of the Gabra6 gene. The 129X1/SvJ x 129S1/Sv-derived R1 ES cell line was used.

Control Suggestions

Approximate Controls

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

Homanics GE; Ferguson C; Quinlan JJ; Daggett J; Snyder K; Lagenaur C; Mi ZP; Wang XH; Grayson DR; Firestone LL. 1997. Gene knockout of the alpha6 subunit of the gamma-aminobutyric acid type A receptor: lack of effect on responses to ethanol, pentobarbital, and general anesthetics. Mol Pharmacol 51(4):588-96PubMed: 9106623 MGI: J:40242

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Genetics

Gabra6^tm1Geh

Allele Symbol: Gabra6^tm1Geh

Allele Name	targeted mutation 1, Gregg E Homanics
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Gabra6, gamma-aminobutyric acid (GABA) A receptor, subunit alpha 6
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	11
Molecular Note	A neomycin selection cassette was inserted into exon 8. Northern blot analysis on RNA derived from cerebellum of homozygous mice demonstrated that aberrant transcripts were expressed from this allele. Hoever, none of these are predicted to be able to code for a functional protein (J:40242). Later studies showed that this mutation also affected the expression of the Gabra1 and Gabrb2 genes (J:63792).
Mutations Made By	Gregg Homanics, University of Pittsburgh

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Neurobiology Research
- Receptor Defects
  - GABA receptor

Genotype: Gabra6^tm1Geh related

Neurobiology Research
- Neurotransmitter Receptor and Synaptic Vesicle Defects
Cell Biology Research
- Channel and Transporter Defects
  - chloride: GABAA receptor
  - chloride

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Gabra6^tm1Geh/Gabra6^tm1Geh
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

homeostasis/metabolism phenotype

abnormal xenobiotic pharmacokinetics
- Normal - behavioral responses to ethanol treatment are not significantly different from controls; functional tolerance, withdrawal hyperexcitability and protracted tolerance tests were similar to both C57BL/6J and 129X1/SvJ control strains
- diazepam, a benzodiazepine drug, displaces all GABA analog binding in the homozygous brain, while this drug does not displace such binding in alpha 6 subunit containing GABA receptors in control brain
- Normal - however, behavioral responses to ethanol, pentobarbitol, halothane and enflurane were not different from controls
- homozygotes exhibit a decrease in the affinity of cerebellar GABA receptors for muscimol, a potent GABA mimetic drug, suggesting that the alpha 6 subunit is responsible for binding this drug

mammalian phenotype

nervous system phenotype
- Normal - immunohistochemical analysis indicates that the general morphology and cytoarchitecture of the cerebellum of knockout mice is similar to controls

homeostasis/metabolism phenotype
- Normal - ability to clear ethanol from the blood did not differ from controls

behavior/neurological phenotype
- Normal - behavioral responses to ethanol treatment are not significantly different from controls; functional tolerance, withdrawal hyperexcitability and protracted tolerance tests were similar to both C57BL/6J and 129X1/SvJ control strains

References

Homanics GE; Ferguson C; Quinlan JJ; Daggett J; Snyder K; Lagenaur C; Mi ZP; Wang XH; Grayson DR; Firestone LL. 1997. Gene knockout of the alpha6 subunit of the gamma-aminobutyric acid type A receptor: lack of effect on responses to ethanol, pentobarbital, and general anesthetics. Mol Pharmacol 51(4):588-96PubMed: 9106623 MGI: J:40242

Additional References

Homanics GE; Le NQ; Kist F; Mihalek R; Hart AR; Quinlan JJ. 1998. Ethanol tolerance and withdrawal responses in GABA(A) receptor alpha 6 subunit null allele mice and in inbred C57BL/6J and strain 129/SvJ mice. Alcohol Clin Exp Res 22(1):259-65PubMed: 9514316 MGI: J:46680

Additional - Gabra6^tm1Geh related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Gabra6-Alternate 1
- Genotyping resources and troubleshooting
Breeding Considerations

This strain can be maintained on a mixed C57BL/6J x 129 genetic background through homozygous sibling matings. The expected coat colors are black and white-bellied agouti.
- Additional Breeding and Husbandry Support
Appearance
- white-bellied agouti
  Related Genotype: A^w/A^w
Citation
When using the B6;129-Gabra6^tm1Geh/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #002710 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Homozygous for Gabra6<tm1Geh>, 1 pair minimum

Related Products and Services

Frozen Mouse Embryo	B6;129-Gabra6<tm1Geh>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6;129-Gabra6<tm1Geh>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6;129-Gabra6<tm1Geh>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6;129-Gabra6<tm1Geh>/J Frozen Embryos	$3373.50

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.

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Gabra6tm1Geh

Allele Symbol: Gabra6tm1Geh

Disease Terms

Research Areas By Phenotype

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

Genotype: Gabra6tm1Geh related

Mammalian Phenotype Terms by Genotype

Genotype: Gabra6tm1Geh/Gabra6tm1Gehinvolves: 129S1/Sv * 129X1/SvJ * C57BL/6

homeostasis/metabolism phenotype

mammalian phenotype

References

Additional References

Additional - Gabra6tm1Geh related

Genotyping Protocols

Breeding Considerations

Appearance

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Gabra6^tm1Geh

Allele Symbol: Gabra6^tm1Geh

Genotype: Gabra6^tm1Geh related

Genotype: Gabra6^tm1Geh/Gabra6^tm1Geh
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Additional - Gabra6^tm1Geh related