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   Donating Investigator Gregg Homanics,   University of Pittsburgh

Description
Mice that are homozygous for the targeted mutation are viable, fertile and normal in size. In contrast to the single S270H knockin, which exhibits increased GABA sensitivity and multiple behavioral and neurological phenotypes, the double S270H L277A mutation restores GABA sensitivity. Western blot analysis indicates an increase in the amount of GABAR subunits alpha3, beta2 , gamma3 and a decrease in alpha1 and beta3. Homozygous mice exhibit an increase in motor activity, but no other overt phenotype. Mutant mice show alterations in some, but not all, behavioral responses to alcohol and general anesthetics.

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 neomycin cassette was inserted upstream of exon 9. The construct was electroporated into 129X1/SvJ-derived Go Germline (Genome Systems) embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6J and the F1 progeny crossed to B6.Cg-Tg(ACTFLPe)9205Dym/J (actin-FLPe) to remove the neo cassette and leave a single FRT site upstream of exon 9. The transgene subsequently was bred out. Heterozygotes were intercrossed to maintain the colony. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Control Information

	Control
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Gabra1

004318

B6.129(FVB)-Gabra1tm1Geh/J

View Strains carrying other alleles of Gabra1     (1 strain)

Phenotype

Phenotype Information

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.

Gabra1^tm4Geh/Gabra1^tm4Geh

        involves: 129X1/SvJ * C57BL/6 * SJL

• behavior/neurological phenotype
• *normal* behavior/neurological phenotype
  • mice do not display seizures, stereotypic behaviors, or aggression   (MGI Ref ID J:144692)
• • hyperactivity
    • mice exhibit greater motor activity in a novel environment than controls; activity is greater both in light and dark phases   (MGI Ref ID J:144692)

View Research Applications

Research Applications

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

Neurobiology Research
Behavioral and Learning Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Gabra1tm4Geh
Allele Name		targeted mutation 4, Gregg E Homanics
Allele Type		Targeted (knock-in)
Common Name(s)		HA;
Mutation Made By		Gregg Homanics,   University of Pittsburgh
Strain of Origin		129X1/SvJ
Gene Symbol and Name		Gabra1, gamma-aminobutyric acid (GABA) A receptor, subunit alpha 1
Chromosome		11
Gene Common Name(s)		ECA4; EJM; EJM5; GABAA alpha 1; Gabra-1;
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 neomycin cassette was inserted upstream of exon 9.Chimeric animals were crossed to C57BL/6J and the F1 progeny crossed to B6.Cg-Tg(ACTFLPe)9205Dym/J (actin-FLPe) to remove the neo cassette and leave a single FRT site upstream of exon 9. [MGI Ref ID J:144692]

Genotyping

Genotyping Information

Genotyping Protocols

Generic Neo Melt Curve Analysis, Melt Curve Analysis
Generic Neo Melt Curve Analysis, Robotic MCA

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Borghese CM; Werner DF; Topf N; Baron NV; Henderson LA; Boehm SL 2nd; Blednov YA; Saad A; Dai S; Pearce RA; Harris RA; Homanics GE; Harrison NL. 2006. An isoflurane- and alcohol-insensitive mutant GABA(A) receptor alpha(1) subunit with near-normal apparent affinity for GABA: characterization in heterologous systems and production of knockin mice. J Pharmacol Exp Ther 319(1):208-18. [PubMed: 16807363]  [MGI Ref ID J:144692]

Additional References

Gabra1^tm4Geh related

Berry RB; Werner DF; Wang X; Jablonski MM; Homanics GE; Mittleman G; Matthews DB. 2008. Mice with targeted genetic reduction of GABA(A) receptor alpha1 subunits display performance differences in Morris water maze tasks. Neurobiol Learn Mem 90(3):580-3. [PubMed: 18625330]  [MGI Ref ID J:154429]

Harris RA; Osterndorff-Kahanek E; Ponomarev I; Homanics GE; Blednov YA. 2011. Testing the silence of mutations: Transcriptomic and behavioral studies of GABA(A) receptor alpha1 and alpha2 subunit knock-in mice. Neurosci Lett 488(1):31-5. [PubMed: 21056629]  [MGI Ref ID J:168344]

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, RG10/RG30.

Colony Maintenance

Breeding & Husbandry	While maintaining a live colony, these mice are bred as homozygotes

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(approximate)
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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