These Adra2a knock-out mice exhibit a resting tachycardia significantly greater than normal and a reduced expression of the adrenergic receptor in the brain.
Dr. Brian Kobilka, Stanford University
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Adra2a | adrenergic receptor, alpha 2a |
Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. Expression of the receptor in the brain was significantly reduced as assessed by antagonist binding, which indicated a 90% reduction. The antagonist binding assay is not entirely specific for the receptor, as the residual 10% binding was attributable to a different subtype of receptor. Mutant mice exhibit a resting tachycardia of more than 180 beats/min greater than normal. Although mutant mice do not have elevated blood pressure, administration of the hypotensive agonist, dexmedetomidine, does not reduce blood pressure. Electrical stimulation of isolated heart atria at frequencies mimicking physiological sympathetic nerve activity results in increased release of noradrenaline at high frequencies and inhibited release at low frequencies. Noradrenaline release from isolated wildtype atria is higher at high frequencies than at low frequencies. Inhibition of neurogenic contraction response to electrical stimulation in isolated vas deferens by dexmedetomidine is reduced in the mutant.
A targeting vector containing neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter and herpes simplex virus thymidine kinase gene was used to disrupt the sequence of the targeted gene encoding the third transmembrane domain. The construct was electroporated into 129X1/SvJ x 129S1/Sv derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were aggregated with 8-cell FVB/N morulae. The resulting chimeric animals were backcrossed to C57BL/6 mice.
Allele Name | targeted mutation 1, Brian K Kobilka |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | alpha2A-; alpha2A-AR-; alpha2A-ARKO; alpha2A-KO |
Gene Symbol and Name | Adra2a, adrenergic receptor, alpha 2a |
Gene Synonym(s) | |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 19 |
Molecular Note | A neomycin cassette inserted into the gene by homologous recombination resulted in a premature stop codon within the third transmembrane domain. Confirmation of the targeting event was demonstrated through Southern analysis. |
Mutations Made By | Dr. Brian Kobilka, Stanford University |
This strain originated on a FVB;129 background, has been backcrossed for 5 generations to C57BL/6 and may be maintained as a homozygote. Donating Investigator reports mutant mice usually have less than 6 litters and less than 6 pups per litter.
When using the α2A-AR KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004367 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or wildtype for Adra2a<tm1Bkk> |
Frozen Mouse Embryo | B6.129-Adra2a<tm1Bkk>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.129-Adra2a<tm1Bkk>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.129-Adra2a<tm1Bkk>/J Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | B6.129-Adra2a<tm1Bkk>/J Frozen Embryos | $3373.50 |
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