Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice.
The oxytocin receptor (OXTR) and its ligand, oxytocin (OXT), regulate reproductive physiology (i.e., parturition and lactation) and sociosexual behaviors. To define the essential functions of OXTR, we generated mice with a null mutation in the Oxtr gene (Oxtr(-/-)) and compared them with OXT-deficient (Oxt(-/-)) mice. Oxtr(-/-) mice were viable and had no obvious deficits in fertility or reproductive behavior. Oxtr(-/-) dams exhibited normal parturition but demonstrated defects in lactation and maternal nurturing. Infant Oxtr(-/-) males emitted fewer ultrasonic vocalizations than wild-type littermates in response to social isolation. Adult Oxtr(-/-) males also showed deficits in social discrimination and elevated aggressive behavior. Ligand Oxt(-/-) males from Oxt(-/-) dams, but not from Oxt(+/-) dams, showed similar high levels of aggression. These data suggest a developmental role for the OXT/OXTR system in shaping adult aggressive behavior. Our studies demonstrate that OXTR plays a critical role in regulating several aspects of social behavior and may have important implications for developmental psychiatric disorders characterized by deficits in social behavior.
Takayanagi
Yuki
Y
Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai, Miyagi 981-8555, Japan.
Yoshida
Masahide
M
Bielsky
Isadora F
IF
Ross
Heather E
HE
Kawamata
Masaki
M
Onaka
Tatsushi
T
Yanagisawa
Teruyuki
T
Kimura
Tadashi
T
Matzuk
Martin M
MM
Young
Larry J
LJ
Nishimori
Katsuhiko
K
D000374:Aggression; D000818:Animals; D005260:Female; D007774:Lactation / Q000235:genetics; D008297:Male; D008425:Maternal Behavior; D051379:Mice; D009154:Mutation; D010121:Oxytocin / Q000172:deficiency / Q000502:physiology; D036801:Parturition; D011247:Pregnancy; D018045:Receptors, Oxytocin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D012920:Social Behavior Disorders / Q000209:etiology* / Q000235:genetics
D018045:Receptors, Oxytocin; D010121:Oxytocin