Takayanagi Yuki, Yoshida Masahide, Bielsky Isadora F, Ross Heather E, Kawamata Masaki, Onaka Tatsushi, Yanagisawa Teruyuki, Kimura Tadashi, Matzuk Martin M, Young Larry J, Nishimori Katsuhiko
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.
Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):16096-101. doi: 10.1073/pnas.0505312102. Epub 2005 Oct 25.
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.
催产素受体（OXTR）及其配体催产素（OXT）调节生殖生理（即分娩和泌乳）以及社会性行为。为了确定OXTR的基本功能，我们构建了Oxtr基因发生无效突变的小鼠（Oxtr(-/-)），并将它们与OXT缺陷型（Oxt(-/-)）小鼠进行比较。Oxtr(-/-)小鼠能够存活，在生育能力或生殖行为方面没有明显缺陷。Oxtr(-/-)母鼠表现出正常分娩，但在泌乳和母性养育方面存在缺陷。幼年Oxtr(-/-)雄性小鼠在受到社会隔离时发出的超声波叫声比野生型同窝小鼠少。成年Oxtr(-/-)雄性小鼠在社会辨别方面也存在缺陷，攻击性行为增加。来自Oxt(-/-)母鼠而非Oxt(+/-)母鼠的配体Oxt(-/-)雄性小鼠表现出类似的高水平攻击性。这些数据表明OXT/OXTR系统在塑造成年期攻击性行为方面具有发育作用。我们的研究表明，OXTR在调节社会行为的多个方面起着关键作用，可能对以社会行为缺陷为特征的发育性精神疾病具有重要意义。
