RGD Reference Report - Granulocyte chemotaxis and disease expression are differentially regulated by GRK subtype in an acute inflammatory arthritis model (K/BxN). - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Granulocyte chemotaxis and disease expression are differentially regulated by GRK subtype in an acute inflammatory arthritis model (K/BxN).

Authors: Tarrant, TK  Rampersad, RR  Esserman, D  Rothlein, LR  Liu, P  Premont, RT  Lefkowitz, RJ  Lee, DM  Patel, DD 
Citation: Tarrant TK, etal., Clin Immunol. 2008 Oct;129(1):115-22. Epub 2008 Jul 26.
RGD ID: 5688373
Pubmed: PMID:18662895   (View Abstract at PubMed)
PMCID: PMC2637521   (View Article at PubMed Central)
DOI: DOI:10.1016/j.clim.2008.06.008   (Journal Full-text)

OBJECTIVE: Chemokine receptors are G-protein coupled receptors (GPCRs) phosphorylated by G-protein receptor kinases (GRKs) after ligand-mediated activation. We hypothesized that GRK subtypes differentially regulate granulocyte chemotaxis and clinical disease expression in the K/BxN model. METHODS: Clinical, histologic, and cytokine responses in GRK6-/-, GRK5-/-, GRK2+/-, and wildtype mice were evaluated using K/BxN serum transfer. Granulocyte chemotaxis was analyzed by transendothelial migration assays. RESULTS: Both GRK6-/- and GRK2+/- mice had increased arthritis disease severity (p<0.001); whereas GRK5-/- was not different from controls. Acute weight loss was enhanced in GRK6-/- and GRK2+/- mice (p<0.001, days 3-10). However, GRK6-/- mice uniquely had more weight loss (>10%), elevated serum IL-6, and enhanced migration toward LTB4 and C5a in vitro. CONCLUSIONS: GRK6 and -2, but not GRK5, are involved in the pathogenesis of acute arthritis in the K/BxN model. In particular, GRK6 may dampen inflammatory responses by regulating granulocyte trafficking toward chemoattractants.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GRK2Humanrheumatoid arthritis  ISOGrk2 (Mus musculus)DNA: deletion: : heterozygousRGD 
GRK5Humanrheumatoid arthritis no_associationISOGrk5 (Mus musculus)DNA: deletion::GRK2 and GRK6 deletions resulted in more severe arthritisRGD 
GRK6Humanrheumatoid arthritis  ISODNA: deletion: : homozygousRGD 
Grk2Ratrheumatoid arthritis  ISOGrk2 (Mus musculus)DNA: deletion: : heterozygousRGD 
Grk2Mouserheumatoid arthritis  IAGP DNA: deletion: : heterozygousRGD 
Grk5Ratrheumatoid arthritis no_associationISOGrk5 (Mus musculus)DNA: deletion::GRK2 and GRK6 deletions resulted in more severe arthritisRGD 
Grk5Mouserheumatoid arthritis no_associationIAGP DNA: deletion::GRK2 and GRK6 deletions resulted in more severe arthritisRGD 
Grk6Ratrheumatoid arthritis  ISODNA: deletion: : homozygousRGD 
Grk6Mouserheumatoid arthritis  IAGP DNA: deletion: : homozygousRGD 

Objects Annotated

Genes (Rattus norvegicus)
Grk2  (G protein-coupled receptor kinase 2)
Grk5  (G protein-coupled receptor kinase 5)
Grk6  (G protein-coupled receptor kinase 6)

Genes (Mus musculus)
Grk2  (G protein-coupled receptor kinase 2)
Grk5  (G protein-coupled receptor kinase 5)
Grk6  (G protein-coupled receptor kinase 6)

Genes (Homo sapiens)
GRK2  (G protein-coupled receptor kinase 2)
GRK5  (G protein-coupled receptor kinase 5)
GRK6  (G protein-coupled receptor kinase 6)


Additional Information