Grk5 (G protein-coupled receptor kinase 5) targeted mutant mice exhibit supersensitivity (lost desensitization) of brain and lung airway M2 muscarinic receptors. Aged homozygotes develop amyloid-like plaques and exhibit some cognitive defects. This strain may be useful in studies of muscarinic receptors and Alzheimer's disease.
Robert Lefkowitz, Duke University Medical Center
Grk5 (G protein-coupled receptor kinase 5) targeted mutant mice exhibit supersensitivity (lost desensitization) of brain and lung airway M2 muscarinic receptors. Aged homozygotes develop amyloid-like plaques and exhibit some cognitive defects. Although the gene is normally expressed in heart and lymphocytes, cardiac M2 muscarinic receptor function and lymphocyte chemotaxis in response to SDF-1 are normal. Homozygotes are viable and present no gross anatomical differences nor striking behavioral abnormalities. Western blot analysis demonstrates a loss of expression in brain, lymphocytes, lung and heart.
Exons 7 and 8 were flanked by loxP sites and a neomycin resistance cassette followed by a loxP site was placed in intron 8. The mutation was created in 129S4/SvJaeSor-derived AK7 embryonic stem (ES) cells. Transient transfection with cre recombinase excised exons 7, 8, and the neomycin resistance cassette. This strain was backcrossed to C57BL/6 for 12 generations by the donating laboratory.
|Allele Name||targeted mutation 1, Robert J Lefkowitz|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||GRK5 KO; grk5-; GRK5-KO|
|Gene Symbol and Name||Grk5, G protein-coupled receptor kinase 5|
|Strain of Origin||129S4/SvJaeSor|
|Molecular Note||A loxP site was inserted upstream of exon 7 and a floxed TK-neo derived cassette was inserted downstream of exon 8 via homologous recombination. Exons 7 and 8 encode critical subelements I, II, and III of the protein kinase catalytical domain. The floxed region containing exons 7 and 8 and the TK-neo cassette was removed by transient expression of cre recombinase in correctly targeted ES cells. Western blot analysis of brain membranes from homozygous mutant animals confirmed the absence of gene expression.|
|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-Grk5tm1Rjl/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010959 in your Materials and Methods section.
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