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The rate-limiting enzyme of 5-HT synthesis, tryptophan hydroxylase (TPH), is encoded by two genes, the well characterized\n                    <jats:italic>tph1<\/jats:italic>\n                    gene and a recently identified\n                    <jats:italic>tph2<\/jats:italic>\n                    gene. In this article, based on the study of a mutant mouse in which the\n                    <jats:italic>tph1<\/jats:italic>\n                    gene has been inactivated by replacement with the \u03b2-galactosidase gene, we establish that the neuronal\n                    <jats:italic>tph2<\/jats:italic>\n                    is expressed in neurons of the raphe nuclei and of the myenteric plexus, whereas the nonneuronal\n                    <jats:italic>tph1<\/jats:italic>\n                    , as detected by \u03b2-galactosidase expression, is in the pineal gland and the enterochromaffin cells. Anatomic examination of the mutant mice revealed larger heart sizes than in wild-type mice. Histological investigation indicates that the primary structure of the heart muscle is not affected. Hemodynamic analyses demonstrate abnormal cardiac activity, which ultimately leads to heart failure of the mutant animals. This report links loss of\n                    <jats:italic>tph1<\/jats:italic>\n                    gene expression, and thus of peripheral 5-HT, to a cardiac dysfunction phenotype. The\n                    <jats:italic>tph1<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    mutant may be valuable for investigating cardiovascular dysfunction observed in heart failure in humans.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2233056100","type":"journal-article","created":{"date-parts":[[2003,11,16]],"date-time":"2003-11-16T15:42:47Z","timestamp":1068997367000},"page":"13525-13530","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":388,"title":["Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral serotonin in cardiac function"],"prefix":"10.1073","volume":"100","author":[{"given":"Francine","family":"C\u00f4t\u00e9","sequence":"first","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire de la Neurotransmission et des Processus Neurod\u00e9g\u00e9n\u00e9ratifs, Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 7091 et Institut F\u00e9d\u00e9ratif de Recherche 70 (Neurosciences), B\u00e2timent CERVI, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, 83, Boulevard de l'H\u00f4pital, 75013 Paris, France; Institut de Myologie et Institut F\u00e9d\u00e9ratif de Recherche 14 (Coeur, Muscle, Vaisseaux), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 582, Centre Hospitalier..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Th\u00e9venot","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire de la Neurotransmission et des Processus Neurod\u00e9g\u00e9n\u00e9ratifs, Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 7091 et Institut F\u00e9d\u00e9ratif de Recherche 70 (Neurosciences), B\u00e2timent CERVI, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, 83, Boulevard de l'H\u00f4pital, 75013 Paris, France; Institut de Myologie et Institut F\u00e9d\u00e9ratif de Recherche 14 (Coeur, Muscle, Vaisseaux), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 582, Centre Hospitalier..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Fligny","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire de la Neurotransmission et des Processus Neurod\u00e9g\u00e9n\u00e9ratifs, Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 7091 et Institut F\u00e9d\u00e9ratif de Recherche 70 (Neurosciences), B\u00e2timent CERVI, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, 83, Boulevard de l'H\u00f4pital, 75013 Paris, France; 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