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Genes & Alleles

Gabra6;   Gabra6tm1Geh;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Stock Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Targeted Mutation Species laboratory mouse Donating Investigator Gregg Homanics,   University of Pittsburgh

Appearance
white-bellied agouti
Related Genotype: A^w/A^w

Strain 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. This 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).

Mammalian Phenotype Terms assigned by genotype Gabra6tm1Geh/Gabra6tm1Geh         involves: 129S1/Sv * 129X1/SvJ * C57BL/6 homeostasis/metabolism phenotype *normal* homeostasis/metabolism phenotype (MGI Ref ID J:46680) ability to clear ethanol from the blood did not differ from controls abnormal pharmacokinetics of xenobiotics (MGI Ref ID J:40242) 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 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 however, behavioral responses to ethanol, pentobarbitol, halothane and enflurane were not different from controls 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 nervous system phenotype *normal* nervous system phenotype (MGI Ref ID J:40242) immunohistochemical analysis indicates that the general morphology and cytoarchitecture of the cerebellum of knockout mice is similar to controls behavior/neurological phenotype *normal* behavior/neurological phenotype (MGI Ref ID J:46680) 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

Gene & Allele Details

Allele Symbol		Gabra6tm1Geh
Allele Name		targeted mutation 1, Gregg E Homanics
Mutation Made By		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		Gabra6, gamma-aminobutyric acid (GABA-A) receptor, subunit alpha 6
Chromosome		11
Gene Common Name(s)		Gabra-6; MGC116903; MGC116904; alpha6;
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). [MGI Ref ID J:40242] [MGI Ref ID J:63792]

Control Information

Allele	Control
Gabra6tm1Geh	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Genotyping Protocols

Gabra6^tm1Geh

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Research Applications

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

Neurobiology Research
Receptor Defects (GABA receptor)

Gabra6^tm1Geh related

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

Neurobiology Research
Neurotransmitter Receptor and Synaptic Vesicle Defects

References

Selected Reference(s)

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):588-96. [PubMed: 9106623]  [MGI Ref ID J:40242]

Additional References

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Price and Supply Information

Strain Name:	B6;129-Gabra6tm1Geh/J
Stock Number:	002710

Price Details

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Supply Details

Standard Supply	Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes	Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. 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 from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.
Licensing	See General Terms and Conditions below
Control Information	View Control Information in Strain Details.

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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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