Strain Name:
129X1.Cg-Gabrb3tm1Uru/Mmucd
Stock Number:
069943-UCD
Citation ID:
RRID:MMRRC_069943-UCD
Other Names:
Gabrb3tm1Uru

Strain Information

Gabrb3tm1Uru
Name: GABRB3, gamma-aminobutyric acid type A receptor subunit beta 3; targeted mutation 1, Uwe Rudolph
Synonyms: Beta3(N265M), beta3N265M
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 7
Alteration at locus: Knock-In
Gabrb3
Name: GABRB3, gamma-aminobutyric acid type A receptor subunit beta 3
Synonyms: Gabrb-3, beta3, A230092K12Rik
Type: Gene
Species: Mouse
Chromosome: 7
Alteration at locus: Knock-In
NCBI: 14402
HGNC: HGNC:4083
Homologene: 633
Genetic Alterations
An asparagine to methionine substitution within the second transmembrane domain was achieved by the introduction of 2 nucleotide substitutions (AAC to ATG) in exon 8 at codon 265 (N265M). A single loxP site remained downstream of exon 8 after a floxed neo cassette was excised via in vivo cre-mediated recombination.
ES Cell Line
R1 derived from (129X1/SvJ x 129S1/Sv)F1-Kitl+
Phenotype
The Gabrb3(N265M) point mutation in the beta3 subunit of the GABA-A receptor very strongly attenuates the response of GABAA receptors containing the beta3 subunit to the general anesthetics etomidate, propofol and pentobarbital, while the sensitivity to the physiological neurotransmitter GABA is largely intact. Sensitivity to the neurosteroidal anesthetics alphaxalone/alphadolone is also maintained. Experiments revealed that the immobilizing and respiratory depressant actions of etomidate and propofol and in part the hypnotic action of these drugs are strongly attenuated in these mice, while the sedative (locomotor activity reducing), hypothermic and heart rate depressant actions of these drugs are preserved.

Conditional phenotype: No.


MeSH Terms
  • Anesthetics, General/metabolism
  • Anesthetics, General/pharmacology
  • Animals
  • Humans
  • Ion Channels/genetics
  • Ion Channels/metabolism
  • Neurons/drug effects
  • Neurons/metabolism
  • Anesthetics, Inhalation/pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Halothane/pharmacology
  • Hindlimb
  • Isoflurane/pharmacology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Mutant Strains
  • Mutation, Missense
  • Protein Subunits/genetics
  • Protein Subunits/physiology
  • Receptors, GABA-A/genetics
  • Receptors, GABA-A/physiology
  • Reflex, Abnormal/drug effects
  • Barbiturates/metabolism
  • Barbiturates/pharmacology
  • Binding Sites/drug effects
  • Binding Sites/physiology
  • Etomidate/metabolism
  • Etomidate/pharmacology
  • Hypnotics and Sedatives/metabolism
  • Hypnotics and Sedatives/pharmacology
  • Mice, Transgenic
  • Mutation/drug effects
  • Mutation/physiology
  • Protein Structure, Secondary
  • Protein Subunits/chemistry
  • Protein Subunits/metabolism
  • Receptors, GABA-A/metabolism
  • Reflex, Righting/drug effects
  • Reflex, Righting/physiology
  • HEK293 Cells
  • Patch-Clamp Techniques
  • Point Mutation
  • Propofol/pharmacology
  • Recombinant Proteins
  • gamma-Aminobutyric Acid/pharmacology
  • Anesthetics, Intravenous/chemistry
  • Anesthetics, Intravenous/pharmacology
  • Etomidate/analogs & derivatives
  • Etomidate/chemistry
  • Photochemistry
  • Stereoisomerism
  • Anesthetics, General/adverse effects
  • Central Nervous System/drug effects
  • Central Nervous System/metabolism
  • Consciousness/drug effects
  • Ion Channel Gating/drug effects
  • Ion Channels/drug effects
  • Mutation
  • Receptors, GABA-A/drug effects
  • Receptors, Glycine/drug effects
  • Receptors, Glycine/genetics
  • Receptors, Glycine/metabolism
Strain Development
The linearized replacement vector was electroporated into R1 ES cells and correctly targeted clones were microinjected into C57BL/6J blastocysts. Chimeric male mice, resulting from a single ES cell clone, were bred with female EIIa-cre mice on the 129/SvJ background to excise the neo cassette from the germline by Cre/loxP-mediated excision. The cre transgene was subsequently bred out, and heterozygous F2 mice were interbred to establish homozygous mutant, heterozygous, and wild-type mice.
Suggested Control Mice
129X1/SvJ
MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@ucdavis.edu. Older strains may not have this information.
Donor
Uwe Rudolph, M.D., University of Illinois at Urbana-Champaign.
Primary Reference

Rudolph U, Antkowiak B. Molecular and neuronal substrates for general anaesthetics. Nat Rev Neurosci. 2004 Sep;5(9):709-20. doi: 10.1038/nrn1496. (Medline PMID: 15322529)

Lambert S, Arras M, Vogt KE, Rudolph U. Isoflurane-induced surgical tolerance mediated only in part by beta3-containing GABA(A) receptors. Eur J Pharmacol. 2005 May 23;516(1):23-7. doi: 10.1016/j.ejphar.2005.04.030. (Medline PMID: 15913600)

Amlong CA, Perkins MG, Houle TT, Miller KW, Pearce RA. Contrasting Effects of the γ-Aminobutyric Acid Type A Receptor β3 Subunit N265M Mutation on Loss of Righting Reflexes Induced by Etomidate and the Novel Anesthetic Barbiturate R-mTFD-MPAB. Anesth Analg. 2016 Nov;123(5):1241-1246. doi: 10.1213/ANE.0000000000001358. Erratum in: Anesth Analg. 2017 Jan;124(1):374. Erratum in: Anesth Analg. 2017 May;124(5):1745. (Medline PMID: 27331778)

Lor C, Perouansky M, Pearce RA. Isoflurane Potentiation of GABAA Receptors Is Reduced but Not Eliminated by the β3(N265M) Mutation. Int J Mol Sci. 2020 Dec 15;21(24):9534. doi: 10.3390/ijms21249534. (Medline PMID: 33333797)

Liao M, Sonner JM, Husain SS, Miller KW, Jurd R, Rudolph U, Eger EI 2nd. R (+) etomidate and the photoactivable R (+) azietomidate have comparable anesthetic activity in wild-type mice and comparably decreased activity in mice with a N265M point mutation in the gamma-aminobutyric acid receptor beta3 subunit. Anesth Analg. 2005 Jul;101(1):131-5, table of contents. doi: 10.1213/01.ANE.0000153011.64764.6F. (Medline PMID: 15976219)

Zeller A, Jurd R, Lambert S, Arras M, Drexler B, Grashoff C, Antkowiak B, Rudolph U. Inhibitory ligand-gated ion channels as substrates for general anesthetic actions. Handb Exp Pharmacol. 2008;(182):31-51. doi: 10.1007/978-3-540-74806-9_2. (Medline PMID: 18175085)

Colony and Husbandry Information

Colony Surveillance Program and Current Health Reports

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@ucdavis.edu.
Coat Color
White
Eye
Pink
MMRRC Breeding System
Other or uncertain
Generation
unknown
Overall Breeding Performance
Excellent
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: 10 to 12 months 10 to 12 months
Average litter size
7 to 9
Recommended wean age
3 Weeks
Average Pups Weaned
4 to 6

Order Request Information

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu for more information.

A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Patrick Sticher.

A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Patrick Sticher

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
069943-UCD-RESUS Litter recovered from cryo-archive $5,055.00 / $8,533.74
Non-Profit / For-Profit
Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu for more information.

Some MMRRC strains were submitted by the donor as cryopreserved germplasm, and because these strains were not cryopreserved by the MMRRC, we have not assessed the quality, nor genotype, of this material. Our expertise in reviving mice from various qualities of frozen sperm and embryos, using methods like IVF and ICSI, gives us confidence in successful recoveries in most cases. However, due to the uncertain quality of these samples, we'll limit revival attempts to two per order. Additional attempts are available for a fee, on top of standard charges, if requested. It's important to note that some strains may lack the expected mutation, so we can't assure successful order fulfillment until we attempt to revive the strain.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.