TARGETED DISRUPTION OF A B-2 BRADYKININ RECEPTOR GENE IN MICE ELIMINATES BRADYKININ ACTION IN SMOOTH-MUSCLE AND NEURONS

Mice that are homozygous for the targeted disruption of the gene encoding the B-2, bradykinin receptor have been generated. The gene disruption results in a deletion of the entire coding sequence for the B-2 receptor. The disruption of the B-2 receptor gene has been confirmed by genetic, biochemical, and pharmacological analyses. Mice that are homozygous for the disruption of the B-2 receptor gene are fertile and indistinguishable from their littermates by visual inspection. Bradykinin fails to produce responses in pharmacological preparations from ileum, uterus, and the superior cervical ganglia from these mice. Therefore, expression of a single gene appears to be responsible for conferring responsiveness to bradykinin in these tissues.