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Genes & Alleles

Gabrd;   Gabrdtm1Geh;

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Product Information

Strain Details

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

Appearance
black
Related Genotype: a/a

Strain Description
Mice that are homozygous null for Gabrd are viable and fertile. Northern blot analysis of -/- adult cerebellar RNA suggests that a chimeric Gabrd /neo transcript is generated from the targeted allele. Western blot analysis fails to detect a Gabrd protein product. Maximal binding for the agonist muscimol was markedly decreased in whole brain homogenates. Consistent with this, in situ autoradiographic analysis indicates a drastic reduction in muscimol binding in most parts of the brain. In general, these mice exhibit a decreased sensitivity to the sedative/hypnotic, anxiolytic and pro-absence effects of neuroactive steroids as determined by sleep time assays, elevated plus-maze assays (measures anxiolytic effect) and the inability of neuroactive steroids to prolong pentylenetetrazol-induced seizures. This decreased sensitivity appears to be selective however, as differential responses to various neuroactive steroids are observed.

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 The following phenotype information may relate to a genetic background differing from this JAX® Mice strain. Gabrdtm1Geh/Gabrdtm1Geh         involves: 129S1/Sv * 129X1/SvJ * C57BL/6J lethality-postnatal postnatal lethality (MGI Ref ID J:64288) only 20.5% of pups weaned are homozygous for the mutation, indicating that ~5% of homozygotes die prior to weaning homeostasis/metabolism phenotype altered response to anesthetics (MGI Ref ID J:64288) an injection of 8 mg/kg of pregnanolone results in a 42% reduction in sleep time in mutants compared to controls altered response to alphaxalone (MGI Ref ID J:64288) Gabrd-deficient mice show a 54% and 38% reduction in sleep time duration to alphaxalone at 8 mg/kg and 16 mg/kg respectively compared to controls behavior/neurological phenotype abnormal contextual conditioning (MGI Ref ID J:110073) percent freezing of female Gabrd-deficient mice is significantly greater than that of wild type during the tone test in a context conditioning paradigm 24 hours after the cued conditioning abnormal cued conditioning behavior (MGI Ref ID J:110073) percent freezing of female Gabrd-deficient mice is significantly greater than that of wild type during trace conditioning absence seizures (MGI Ref ID J:64288) ganaxolone failed to prolong PTZ-induced absence-like seizures in null mice but increased freezing 74% in controls decreased anxiety-related response (MGI Ref ID J:64288) mutants display fewer open arm entries in the elevated plus maze; injection of ganaxolone to wild type mice resulted in a 2-fold increase in open arm entries but had no effect on mutants nervous system phenotype abnormal inhibitory postsynaptic currents (MGI Ref ID J:64288) decay time of mini IPSCs is faster in mutants than in wild type controls absence seizures (MGI Ref ID J:64288) ganaxolone failed to prolong PTZ-induced absence-like seizures in null mice but increased freezing 74% in controls reproductive system phenotype decreased litter size (MGI Ref ID J:64288) in the F3 generation, homozygous matings produced statistically fewer pups (6.3 pups/litter) than wild type pairs (7.6 pups/litter) Gabrdtm1Geh/Gabrdtm1Geh         involves: 129S1/Sv * 129X1/SvJ * C57BL/6 hearing/vestibular/ear phenotype *normal* hearing/vestibular/ear phenotype (MGI Ref ID J:112951) at 6 weeks of age, homozygotes show no signs of cochlear pathology, with normal hearing sensitivity, as determined by ABR/DPOAE assays across various test frequencies, and normal OHC efferent function, as assessed by measuring DPOAE suppression caused by efferent-bundle shocks

Gene & Allele Details

Allele Symbol		Gabrdtm1Geh
Allele Name		targeted mutation 1, Gregg E Homanics
Common Name(s)		delta-;
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		Gabrd, gamma-aminobutyric acid (GABA-A) receptor, subunit delta
Chromosome		4
Gene Common Name(s)		AI853201; GABAA-RD; MGC105467; MGC45284; expressed sequence AI853201;
Molecular Note		Insertion of a MC1-neomycin resistance cassette into exon 4 disrupted the gene. Northern blot analysis of cerebellar total RNA from homozygous mutant adult mice detected moderate levels of a novel 2.3kb transcript but not the 1.9kb wild type transcript. Western blot analysis of cerebellar membranes did not detect the wild type protein in homozygous mutant mice. [MGI Ref ID J:64288]

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Genotyping Protocols

Gabrd^tm1Geh
NEOTD (Generic Neo)

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Additional Web Information

Congenic Nomenclature

Research Applications

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

Neurobiology Research
Receptor Defects (GABA receptor)

Gabrd^tm1Geh related

Neurobiology Research
Neurotransmitter Receptor and Synaptic Vesicle Defects

References

Selected Reference(s)

Mihalek RM; Banerjee PK; Korpi ER; Quinlan JJ; Firestone LL; Mi ZP; Lagenaur C; Tretter V; Sieghart W; Anagnostaras SG; Sage JR; Fanselow MS; Guidotti A; Spigelman I; Li Z; DeLorey TM; Olsen RW; Homanics GE. 1999. Attenuated sensitivity to neuroactive steroids in gamma-aminobutyrate type A receptor delta subunit knockout mice. Proc Natl Acad Sci U S A 96(22):12905-10. [PubMed: 10536021]  [MGI Ref ID J:64288]

Additional References

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Price and Supply Information

Strain Name:	B6.129-Gabrdtm1Geh/J
Stock Number:	003725

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	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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