Mice that are homozygous for this knockout of the Adora2a gene, are resistant to experimentally induced ischemic brain injury and exhibit increased resistance to the addictive substances amphetamine and cocaine.
Joel Linden, University of Virginia
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No functional gene product (protein) is detected by receptor autoradiography analysis of the brain. Experimentally induced cerebral infarction volume and resulting neurological function impairment are reduced in homozygotes. Treatment with receptor agonist, CGS 21680, does not elicit decreased locomotor activity in homozygotes, as compared to wildtype. Homozygotes have reduced spontaneous activity and increased resistance to the addictive substances amphetamine and cocaine. This mutant mouse strain may be useful in studies of behavior, ischemic brain injury, stroke, responses to addictive substances and T cell response to inflammation.
A targeting vector containing PGKneo cassette was used to disrupt the 3' portion of exon 2 and intron 2. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to 129/SvEvTac mice, and then been backcrossed to BALB/cJ for 2 generations (using a speed congenic protocol) before arriving at The Jackson Laboratory. The mice were crossed to BALB/cJ once to establish the colony.
|Allele Name||targeted mutation 1, Jiang-Fan Chen|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||A2A; A2A KO; A2AAR-; A2aR-; A2AR KO; Adora2atm1Chren; gKO|
|Gene Symbol and Name||Adora2a, adenosine A2a receptor|
|Strain of Origin||129S4/SvJae|
|Molecular Note||Part of exon 2 and intron 2 was replaced by a neomycin selection cassette. The absence of functional protein was demonstrated in homozygous mice by in situ binding assays and neurochemical tests.|
|Mutations Made By|| |
Vanessa Hajzus, University of Virginia
When maintaining a live colony, these mice can be bred as homozygotes.
When using the A2A KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #010685 in your Materials and Methods section.