These Grk6 targeted mutant mice exhibit supersensitive locomotor responses to psychostimulant drugs and dopamine D2 agonists. These mice may be useful in studies of dopaminergic transmission, immune cell chemotaxis, and colitis.
Robert Lefkowitz, Duke University Medical Center
These Grk6 (G protein-coupled receptor kinase 6) targeted mutant mice exhibit supersensitive locomotor responses to psychostimulant drugs and dopamine D2 agonists. CXCL12-induced chemotaxis of B and T lymphocytes from homozygous mice is reduced in vitro, whereas neutrophils show enhanced accumulation at sites of inflammation. In the dextran sulfate model of colitis, homozygotes develop more severe disease and fail to recover normal colonic function after withdrawal of the irritant.
Exons 3-9 were flanked by loxP sites and a loxP-neomycin resistance cassette was placed in intron 2. The mutation was created in 129S4/SvJaeSor-derived AK7 embryonic stem (ES) cells. Chimeras were crossed with C57BL/6 and resultant animals were crossed with a C57BL/6 background CMV-cre strain to excise both the neomycin cassette and exons 3-9. This strain was backcrossed to C57BL/6 for more than 12 generations by the donating laboratory.
|Allele Name||targeted mutation 1.1, Marc G Caron|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||GRK6-; GRK6 KO; GRK6-KO|
|Gene Symbol and Name||Grk6, G protein-coupled receptor kinase 6|
|Strain of Origin||129S4/SvJaeSor|
|Molecular Note||The floxed region containing the neo-tk cassette and exons 3 through 9 was excised via cre mediated recombination in the germline. Protein was undetected by Western blot analysis of brainstem and striatum tissue obtained from homozygous mutant mice. Immunostaining confirmed the absence of protein in homozygous mutant striatal neurons.|
|Mutations Made By|| |
Richard Premont, Duke University Medical Center
When maintained as a live colony, homozygotes or heterozygotes may be bred.
When using the B6.129S4-Grk6tm1.1Mca/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010961 in your Materials and Methods section.