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| 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. | |||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote (Female x Male) 16-FEB-11 Species laboratory mouse Generation N13+F5 (30-JUN-11)
Generation DefinitionsDonating Investigator Robert Lefkowitz, Duke University Medical Center Description
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.Development
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.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Alzheimer's Disease Models
View Alzheimer's Disease Models (108 strains)
005808 B6.129P2-Grk5tm1Dgen/J 010960 B6.129S4-Grk5tm2Rjl/J
Additional Web Information
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Grk5tm1Rjl/Grk5tm1Rjl
involves: 129S4/SvJaeSor * C57BL/6
- homeostasis/metabolism phenotype
- decreased body temperature
- greater and longer lasting body temperature depression in response to muscarinic agonists (oxotremorine) (MGI Ref ID J:59179)
- decreased core body temperature
- core body temperature is about 0.9oC lower than controls (MGI Ref ID J:59179)
- behavior/neurological phenotype
- decreased thermal nociceptive threshold
- hypoactivity
- greater and longer lasting depression of horizontal activity in response to muscarinic agonists (oxotremorine) (MGI Ref ID J:59179)
- tremors
- increased and prolonged tremors in response to muscarinic agonists (oxotremorine) (MGI Ref ID J:59179)
- nervous system phenotype
- abnormal CNS synaptic transmission
- muscarinic receptors in the brain stem are resistant to desensitization (MGI Ref ID J:59179)
- digestive/alimentary phenotype
- increased salivation
- in response to muscarinic agonists (oxotremorine) (MGI Ref ID J:59179)
- respiratory system phenotype
- increased airway responsiveness
- tracheal airway hyperresponsive to vagal stimulation as measured by airway pressure time index (APTI) (MGI Ref ID J:96208)
- muscle phenotype
- abnormal muscle contractility
- M2 receptors of smooth muscle in the tracheal airway are desensitized (MGI Ref ID J:96208)
- endocrine/exocrine gland phenotype
- increased salivation
- in response to muscarinic agonists (oxotremorine) (MGI Ref ID J:59179)
- integument phenotype
- decreased thermal nociceptive threshold
This mouse can be used to support research in many areas including:
Neurobiology Research
Alzheimer's Disease
Behavioral and Learning Defects
Receptor Defects
cholinergic receptor
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Grk5tm1Rjl | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Robert J Lefkowitz | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | GRK5 KO; GRK5-KO; grk5-; | ||
| Mutation Made By | Richard Premont, Duke University Medical Center | ||
| Strain of Origin | 129S4/SvJaeSor | ||
| Gene Symbol and Name | Grk5, G protein-coupled receptor kinase 5 | ||
| Chromosome | 19 | ||
| Gene Common Name(s) | G protein-receptor coupled kinase 5; GPRK5; Gprk5; | ||
| 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 floxedregion 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. [MGI Ref ID J:59179] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Grk5tm1Rjl, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Gainetdinov RR; Bohn LM; Walker JK; Laporte SA; Macrae AD; Caron MG; Lefkowitz RJ; Premont RT. 1999. Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice. Neuron 24(4):1029-36. [PubMed: 10624964] [MGI Ref ID J:59179]
Additional References
Grk5tm1Rjl relatedChen Y; Wang F; Long H; Chen Y; Wu Z; Ma L. 2011. GRK5 promotes F-actin bundling and targets bundles to membrane structures to control neuronal morphogenesis. J Cell Biol 194(6):905-20. [PubMed: 21930777] [MGI Ref ID J:177727]
Cheng S; Li L; He S; Liu J; Sun Y; He M; Grasing K; Premont RT; Suo WZ. 2010. GRK5 deficiency accelerates {beta}-amyloid accumulation in Tg2576 mice via impaired cholinergic activity. J Biol Chem 285(53):41541-8. [PubMed: 21041302] [MGI Ref ID J:167361]
Fong AM; Premont RT; Richardson RM; Yu YR; Lefkowitz RJ; Patel DD. 2002. Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice. Proc Natl Acad Sci U S A 99(11):7478-83. [PubMed: 12032308] [MGI Ref ID J:76872]
Liu J; Rasul I; Sun Y; Wu G; Li L; Premont RT; Suo WZ. 2009. GRK5 deficiency leads to reduced hippocampal acetylcholine level via impaired presynaptic M2/M4 autoreceptor desensitization. J Biol Chem 284(29):19564-71. [PubMed: 19478075] [MGI Ref ID J:152271]
Martini JS; Raake P; Vinge LE; DeGeorge B Jr; Chuprun JK; Harris DM; Gao E; Eckhart AD; Pitcher JA; Koch WJ. 2008. Uncovering G protein-coupled receptor kinase-5 as a histone deacetylase kinase in the nucleus of cardiomyocytes. Proc Natl Acad Sci U S A 105(34):12457-62. [PubMed: 18711143] [MGI Ref ID J:138970]
Rajagopal K; Whalen EJ; Violin JD; Stiber JA; Rosenberg PB; Premont RT; Coffman TM; Rockman HA; Lefkowitz RJ. 2006. Beta-arrestin2-mediated inotropic effects of the angiotensin II type 1A receptor in isolated cardiac myocytes. Proc Natl Acad Sci U S A 103(44):16284-9. [PubMed: 17060617] [MGI Ref ID J:115598]
Suo Z; Cox AA; Bartelli N; Rasul I; Festoff BW; Premont RT; Arendash GW. 2007. GRK5 deficiency leads to early Alzheimer-like pathology and working memory impairment. Neurobiol Aging 28(12):1873-88. [PubMed: 17011668] [MGI Ref ID J:129560]
Tarrant TK; Rampersad RR; Esserman D; Rothlein LR; Liu P; Premont RT; Lefkowitz RJ; Lee DM; Patel DD. 2008. Granulocyte chemotaxis and disease expression are differentially regulated by GRK subtype in an acute inflammatory arthritis model (K/BxN). Clin Immunol 129(1):115-22. [PubMed: 18662895] [MGI Ref ID J:140405]
Walker JK; Gainetdinov RR; Feldman DS; McFawn PK; Caron MG; Lefkowitz RJ; Premont RT; Fisher JT. 2004. G protein-coupled receptor kinase 5 regulates airway responses induced by muscarinic receptor activation. Am J Physiol Lung Cell Mol Physiol 286(2):L312-9. [PubMed: 14565944] [MGI Ref ID J:96208]
Wu JH; Goswami R; Cai X; Exum ST; Huang X; Zhang L; Brian L; Premont RT; Peppel K; Freedman NJ. 2006. Regulation of the platelet-derived growth factor receptor-beta by G protein-coupled receptor kinase-5 in vascular smooth muscle cells involves the phosphatase Shp2. J Biol Chem 281(49):37758-72. [PubMed: 17018529] [MGI Ref ID J:117638]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintained as a live colony, homozygotes or heterozygotes may be bred. Mating System Homozygote x Homozygote (Female x Male) 16-FEB-11
Purchasing information
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
 |
Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $172.00 Female or Male Homozygous for Grk5tm1Rjl
Pairs /Price (US dollars $) Pair Genotype $344.00 Homozygous for Grk5tm1Rjl x Homozygous for Grk5tm1Rjl Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
|
Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $223.60 Female or Male Homozygous for Grk5tm1Rjl
Pairs /Price (US dollars $) Pair Genotype $447.20 Homozygous for Grk5tm1Rjl x Homozygous for Grk5tm1Rjl Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
|
|
|
Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
General Supply Notes
- This strain is included in the Induced Mutant Resource Colony collection.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.Ordering Information
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