Growth retardation and altered autonomic control in mice lacking brain serotonin.
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.
Alenina
Natalia
N
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Kikic
Dana
D
Todiras
Mihail
M
Mosienko
Valentina
V
Qadri
Fatimunnisa
F
Plehm
Ralph
R
Boyé
Philipp
P
Vilianovitch
Larissa
L
Sohr
Reinhard
R
Tenner
Katja
K
Hörtnagl
Heide
H
Bader
Michael
M
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*
D012701:Serotonin; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase