Transgenic mice whose γ 1 and κ genes have been replaced by human ε and κ genes (HYP3P.402)

Abstract

Abstract IgE is a primary mediator in most allergic diseases. Human IgE specific for various allergens are very important reagents in diagnostic assays for the management of allergic diseases. However, allergen-specific human IgEs are present in patients’ blood at very low levels and hence extremely difficult to prepare. We have now constructed a transgenic homozygous mouse strain, referred to as HεκKI strain, whose γ1 constant region gene segment has been replaced by human ε gene constant region segment and whose κ constant gene replaced by human κ constant gene. In those HεκKI mice, the human IgE levels are about 10 times of mouse IgE. Upon immunization with an allergen papain, both human IgE and mouse IgE were increased, with human IgE increased to about 30 folds of mouse IgE. We have prepared a number of hybridomas secreting monoclonal human IgE (the variable regions being mouse) specific for papain. Cells of a basophilic leukemic line pulsed with such human IgE could be activated by papain to undergo degranulation process. These results indicate that the transgenic mouse strain HεκKI could be employed to prepare polyclonal and monoclonal human IgE specific for various allergens.