An isoform specific disruption of the endogenous allele was achieved by the insertion of neomycin and thymidine kinase cassettes via homologous recombination. The disruption putatively resulted in functional ablation in the peripheral tissues. The endogenous allele encodes the rate-limiting enzyme for serotonin synthesis, and while serotonin was detected at normal levels in the brain, it was absent in the periphery, with the exception of low levels (4% of wild-type) detected in the duodenum.