title: An oral sensitization model in Brown Norway rats to screen for potential allergenicity of food proteins.
abstract: We developed an oral sensitization protocol for food proteins for the rat. Young Brown Norway (BN) rats were exposed to 1 mg ovalbumin (OVA) by daily gavage dosing for 42 days without the use of an adjuvant. OVA-specific IgE and IgG responses were determined by ELISA. On an oral challenge with OVA some clinical symptoms of food allergy-like effects on the respiratory system, blood pressure, and permeability of the gastrointestinal barrier were studied. In addition, BN rats were orally exposed to a total hen egg white protein (HEW) extract and cow's milk (CM) and the specificities of induced antibody responses were compared with the specificities of antibodies in sera from egg- and milk-allergic patients using immunoblotting. Animals orally exposed to the allergens developed specific IgE and IgG antibodies which recognized the same proteins compared with antibodies from egg- or CM-allergic patients. Among the various clinical symptoms of food allergy, gut permeability was increased after an oral challenge. In addition, some animals demonstrated a temporary decrease in breathing frequency or systolic blood pressure. The results obtained show that the Brown Norway rat is a suitable animal model for inducing specific IgG and IgE responses on daily intragastric dosing of OVA without the use of an adjuvant. Moreover, local immune-mediated effects on oral challenge are observed. The observation that enterally exposed BN rats and food-allergic patients demonstrate antibody responses to a comparable selection of proteins on exposure to different protein mixtures (HEW and CM) further supports the suitability of the BN rat as an animal model for food allergy research and for the study of the allergenicity of (novel) food proteins.
authors.affiliation: Department of Target Organ Toxicology, TNO Nutrition and Food Research Institute, AJ Zeist, 3700, The Netherlands. Knippels@voeding.tno.nl
authors.forename: L M
authors.initials: LM
authors.lastname: Knippels
authors.forename: G F
authors.initials: GF
authors.lastname: Houben
authors.forename: S
authors.initials: S
authors.lastname: Spanhaak
authors.forename: A H
authors.initials: AH
authors.lastname: Penninks
mesh_terms: D000284:Administration, Oral; D000485:Allergens / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000906:Antibodies / Q000097:blood; D001794:Blood Pressure; D002417:Cattle; D002645:Chickens; D004044:Dietary Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity*; D004064:Digestive System / Q000276:immunology / Q000503:physiopathology; D004195:Disease Models, Animal; D004527:Egg Proteins / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D005512:Food Hypersensitivity / Q000209:etiology* / Q000276:immunology; D006801:Humans; D007114:Immunization; D007158:Immunologic Techniques; D008297:Male; D008894:Milk Proteins / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D010323:Passive Cutaneous Anaphylaxis; D051381:Rats; D011914:Rats, Inbred BN; D012129:Respiratory Function Tests
chemical_list: D000485:Allergens; D000906:Antibodies; D004044:Dietary Proteins; D004527:Egg Proteins; D008894:Milk Proteins; D010047:Ovalbumin