These Arrb2 (arrestin, beta 2) knock-out mice show a significantly increased potentiation and prolongation of the analgesic effect of morphine, and may be useful in studies of pain and analgesia.
Robert Lefkowitz, Duke University Medical Center
Homozygous Arrb2 (arrestin, beta 2) targeted mutation mice show a significantly increased potentiation and prolongation of the analgesic effect of morphine, suggesting that μ opioid receptor desensitization is impaired. They lack expression of the gene as determined by immunoblot of brainstem, periaqueductal gray tissue, spleen, lung, and skin. These mice may be useful in studies of pain and analgesia.
A targeting vector was designed to insert a neomycin resistance cassette and delete exon 2 of the beta-arrestin 2 gene Arrb2) on chromosome 11. This strain was created in a 129-derived embryonic stem cell line. Mutant mice were backcrossed to C57BL/6 for more than ten generations by the donating laboratory (see SNP results below) prior to sending males to The Jackson Laboratory Repository in 2012. Upon arrival, males were used to cryopreserve sperm. To establish the living mouse colony, an aliquot of the frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the living colony at The Jackson Laboratory Repository. This revealed 2 of 27 markers, one each on chromosomes 1 and 2, that were not fixed for C57BL/6 allele-type (e.g.: still segregating for 129 allele-type markers). In addition, 1 marker on chromosome 17 (~34 Mbp) was found to be segregating for a marker of unknown genetic contribution. These data suggest the mice may have been backcrossed to C57BL/6 for fewer generations than reported prior to arrival at The Jackson Laboratory.
|Allele Name||targeted mutation 1, Robert J Lefkowitz|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Arr3-; Arrb2-; betaarr2-; betarr2-KO|
|Gene Symbol and Name||Arrb2, arrestin, beta 2|
|Strain of Origin||129X1/SvJ|
|Molecular Note||PGK-neomycin cassette replaced the entire second exon. This resulted in the deletion of amino acids 9-19. The absence of protein was demonstrated by immunoblotting of extracts from brainstem, periaqueductal gray tissue, spleen, lung, and skin.|
|Mutations Made By|| |
Robert Lefkowitz, Duke University Medical Center
When maintained as a live colony, homozygotes or heterozygotes may be bred.
When using the βarr2-KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #011130 in your Materials and Methods section.
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