{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T01:01:49Z","timestamp":1793322109113,"version":"4.5.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"32","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,8,9]]},"abstract":"<jats:p>\n                    Serotonin (5-HT) has long been recognized as a neurotransmitter in the central nervous system, where it modulates a variety of behavioral functions. Availability of 5-HT depends on the expression of the enzyme tryptophan hydroxylase (TPH), and the recent discovery of a dual system for 5-HT synthesis in the brain (TPH2) and periphery (TPH1) has renewed interest in studying the potential functions played by 5-HT in nonnervous tissues. Moreover, characterization of the TPH1 knockout mouse model (TPH1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) led to the identification of unsuspected roles for peripheral 5-HT, revealing the importance of this monoamine in regulating key physiological functions outside the brain. Here, we present in vivo data showing that mice deficient in peripheral 5-HT display morphological and cellular features of ineffective erythropoiesis. The central event occurs in the bone marrow where the absence of 5-HT hampers progression of erythroid precursors expressing 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    and 5-HT\n                    <jats:sub>2B<\/jats:sub>\n                    receptors toward terminal differentiation. In addition, red blood cells from 5-HT\u2013deficient mice are more sensitive to macrophage phagocytosis and have a shortened in vivo half-life. The combination of these two defects causes TPH1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    animals to develop a phenotype of macrocytic anemia. Direct evidence for a 5-HT effect on erythroid precursors is provided by supplementation of the culture medium with 5-HT that increases the proliferative capacity of both 5-HT\u2013deficient and normal cells. Our thorough analysis of TPH1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice provides a unique model of morphological and functional aberrations of erythropoiesis and identifies 5-HT as a key factor for red blood cell production and survival.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1103964108","type":"journal-article","created":{"date-parts":[[2011,7,26]],"date-time":"2011-07-26T00:02:29Z","timestamp":1311638549000},"page":"13141-13146","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":75,"title":["Ineffective erythropoiesis with reduced red blood cell survival in serotonin-deficient mice"],"prefix":"10.1073","volume":"108","author":[{"given":"Pascal","family":"Amireault","sequence":"first","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Descartes, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 8147, H\u00f4pital Necker, 75743 Paris Cedex 15, France;"},{"name":"Biotechnology and Biotherapy Laboratory, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epini\u00e8re, Universit\u00e9 Pierre et Marie Curie, UPMC\/Inserm Unit\u00e9 Mixte de Recherche S 975, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 7225, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, 75013 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Hatia","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Descartes, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 8147, H\u00f4pital Necker, 75743 Paris Cedex 15, France;"},{"name":"Biotechnology and Biotherapy Laboratory, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epini\u00e8re, Universit\u00e9 Pierre et Marie Curie, UPMC\/Inserm Unit\u00e9 Mixte de Recherche S 975, Centre National de la Recherche Scientifique Unit\u00e9 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et Institut National de Recherche Agronomique Unit\u00e9 Mixte de Recherche 955, Ecole Nationale V\u00e9t\u00e9rinaire d'Alfort, 94704 Maisons-Alfort Cedex, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Collet","sequence":"additional","affiliation":[{"name":"Service de Biochimie, Assistance Publique H\u00f4pitaux de Paris, AP-HP, H\u00f4pital Lariboisi\u00e8re, 75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Callebert","sequence":"additional","affiliation":[{"name":"Service de Biochimie, Assistance Publique H\u00f4pitaux de Paris, AP-HP, H\u00f4pital Lariboisi\u00e8re, 75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marie","family":"Launay","sequence":"additional","affiliation":[{"name":"Service de Biochimie, Assistance Publique H\u00f4pitaux de Paris, AP-HP, H\u00f4pital Lariboisi\u00e8re, 75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Hermine","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Descartes, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 8147, H\u00f4pital Necker, 75743 Paris Cedex 15, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Schneider","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Descartes, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 8147, H\u00f4pital Necker, 75743 Paris Cedex 15, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Mallet","sequence":"additional","affiliation":[{"name":"Biotechnology and Biotherapy Laboratory, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epini\u00e8re, Universit\u00e9 Pierre et Marie Curie, UPMC\/Inserm Unit\u00e9 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