Numbers of total and dopaminergic enteric neurons are decreased in mice that lack TPH2 or TPH1 and TPH2. A, The total number of neurons was obtained from counts made in whole mounts of dissected laminar preparations of longitudinal muscle with adherent myenteric plexus. The immunocytochemical detection of HuC/D was used as a neuronal marker. The numbers of total enteric neurons in TPH1KO, TPH2KO, and TPH1/2dKO mice were compared, respectively, with those of their wild-type littermates. Significantly fewer total neurons were found in TPH2KO and TPH1/2dKO animals than in their wild-type littermates; however, the total number of neurons in TPH1KO mice was not significantly different from that in their wild-type littermates. The number of neurons in TPH1/2dKO animals did not significantly differ from that in mice lacking only TPH2. B, TH was identified immunocytochemically and used as a marker for enteric dopaminergic neurons. Preparations were the same as used to investigate total neuronal numbers. Again, the numbers of TH-immunoreactive neurons in TPH1KO, TPH2KO, and TPH1/2dKO mice were compared with those of their respective wild-type littermates. The numbers of enteric dopaminergic neurons were significantly reduced in TPH2KO and TPH1/2dKO animals; however, the numbers of dopaminergic neurons in TPH1KO mice did not differ significantly from that of their wild-type littermates. The numbers of dopaminergic neurons in TPH1/2dKO animals was not significantly different from those in mice lacking only TPH2. Although both total and dopaminergic neurons were reduced in mice lacking TPH2 and TPH1 and TPH2, the deficit in dopaminergic neurons was more severe than that in total neurons. C, D, Neurons immunostained with antibodies to HuC/D in wild-type littermates (C) and TPH1/2dKO mice (D). E, F, Neurons immunostained with antibodies to TH in wild-type littermates (E) and TPH1/2dKO mice (F). G, H, Neurons immunostained with antibodies to HuC/D in wild-type littermates (G) and TPH2KO mice (H). I, J, Neurons immunostained with antibodies to TH in wild-type littermates (I) and TPH2KO mice (F). Neurons immunostained with antibodies to HuC/D in wild-type littermates (K) and TPH1KO mice (L). M, N, Neurons immunostained with antibodies to TH in wild-type littermates (M) and TPH1KO mice (N). Scale bars: L, 50 μm (for all HuC/D images); N, 25 μm (for all TH images). ns, Not significant.