RGD Reference Report - Amelioration of chronic and spontaneous intestinal inflammation with an antisense oligonucleotide (ISIS 9125) to intracellular adhesion molecule-1 in the HLA-B27/beta2 microglobulin transgenic rat model. - 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   new 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

Amelioration of chronic and spontaneous intestinal inflammation with an antisense oligonucleotide (ISIS 9125) to intracellular adhesion molecule-1 in the HLA-B27/beta2 microglobulin transgenic rat model.

Authors: Bowen-Yacyshyn, MB  Bennett, CF  Nation, N  Rayner, D  Yacyshyn, BR 
Citation: Bowen-Yacyshyn MB, etal., J Pharmacol Exp Ther 2002 Sep;302(3):908-17.
RGD ID: 729408
Pubmed: PMID:12183646   (View Abstract at PubMed)
DOI: DOI:10.1124/jpet.102.036053   (Journal Full-text)

Adhesion molecules are known to be an important part of leukocyte migration and extravasation in both homeostatic and inflammatory conditions. Intracellular adhesion molecule-1 (ICAM-1 or CD54) is constitutively expressed on endothelial cells and is up-regulated during acute and chronic inflammation. We investigated the efficacy and consequences of interfering with CD54 after administration of an antisense oligonucleotide to ICAM-1 (CD54) in the transgenic HLA-B27/beta2 microglobulin rat model. One hundred percent of the HLA-B27 transgene + animals will spontaneously develop chronic inflammation (some more severely than others) in the gastric mucosa, cecum, and colon. We carried out two studies, i.p. injection and rectal administration of antisense. Following i.p. and rectal treatment, there were significant decreases in colonic mucosal wall thickness, histologic inflammation, CD54 expression in the colon and peripheral blood, and the percentage of colon weight per end body weight. Furthermore, decreased expression of CD49d, CD18, and tumor necrosis factor-alpha was observed in antisense treated rats. Therefore, the HLA-B27 transgenic model of spontaneous and chronic inflammatory bowel disease, which has increased expression of adhesion molecules, responds to both routes of administration of ICAM-1 antisense oligonucleotides. These studies support the regulatory role of adhesion molecules in chronic intestinal inflammation, the need for an understanding of how the route of drug delivery can alter the dose and area affected, and finally the role of antisense oligonucleotides as a therapeutic modality in chronic spontaneous inflammatory bowel diseases.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Colitis  ISOItga4 (Rattus norvegicus)729408; 729408protein:increased expression:colon (rat)RGD 
Experimental Colitis  IEP 729408protein:increased expression:colon (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
leukocyte migration  TAS 729408 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Icam1  (intercellular adhesion molecule 1)
Itga4  (integrin subunit alpha 4)

Genes (Mus musculus)
Itga4  (integrin alpha 4)

Genes (Homo sapiens)
ITGA4  (integrin subunit alpha 4)


Additional Information