title: Growth retardation and altered autonomic control in mice lacking brain serotonin.
abstract: Serotonin synthesis in mammals is initiated by 2 distinct tryptophan hydroxylases (TPH), TPH1 and TPH2. By genetically ablating TPH2, we created mice (Tph2(-/-)) that lack serotonin in the central nervous system. Surprisingly, these mice can be born and survive until adulthood. However, depletion of serotonin signaling in the brain leads to growth retardation and 50% lethality in the first 4 weeks of postnatal life. Telemetric monitoring revealed more extended daytime sleep, suppressed respiration, altered body temperature control, and decreased blood pressure (BP) and heart rate (HR) during nighttime in Tph2(-/-) mice. Moreover, Tph2(-/-) females, despite being fertile and producing milk, exhibit impaired maternal care leading to poor survival of their pups. These data confirm that the majority of central serotonin is generated by TPH2. TPH2-derived serotonin is involved in the regulation of behavior and autonomic pathways but is not essential for adult life.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
authors.forename: Dana
authors.initials: D
authors.lastname: Kikic
authors.forename: Mihail
authors.initials: M
authors.lastname: Todiras
authors.forename: Valentina
authors.initials: V
authors.lastname: Mosienko
authors.forename: Fatimunnisa
authors.initials: F
authors.lastname: Qadri
authors.forename: Ralph
authors.initials: R
authors.lastname: Plehm
authors.forename: Philipp
authors.initials: P
authors.lastname: Boyé
authors.forename: Larissa
authors.initials: L
authors.lastname: Vilianovitch
authors.forename: Reinhard
authors.initials: R
authors.lastname: Sohr
authors.forename: Katja
authors.initials: K
authors.lastname: Tenner
authors.forename: Heide
authors.initials: H
authors.lastname: Hörtnagl
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000503:physiopathology*; D001794:Blood Pressure; D001831:Body Temperature / Q000235:genetics; D001921:Brain / Q000201:enzymology*; D006130:Growth Disorders / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D006339:Heart Rate; D051379:Mice; D018345:Mice, Knockout; D012119:Respiration; D012701:Serotonin / Q000096:biosynthesis / Q000172:deficiency*; D012890:Sleep / Q000235:genetics; D016615:Telomere / Q000235:genetics / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism*
chemical_list: D012701:Serotonin; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase