Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice

Yuki Takayanagi, Masahide Yoshida, Isadora F. Bielsky, Heather E. Ross, Masaki Kawamata, Tatsushi Onaka, Teruyuki Yanagisawa, Tadashi Kimura, Martin M. Matzuk, Larry J. Young, Katsuhiko Nishimori

Research output: Contribution to journalArticle

442 Citations (Scopus)

Abstract

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 Oxtr-/- 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.

Original languageEnglish
Pages (from-to)16096-16101
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number44
DOIs
Publication statusPublished - Nov 1 2005

Fingerprint

Oxytocin Receptors
Parturition
Oxytocin
Social Behavior
Genes
Lactation
Social Discrimination
Ligands
Reproductive Behavior
Social Isolation
Aggression
Ultrasonics
Fertility
Psychiatry
Mothers
mouse OXTR protein
Mutation

All Science Journal Classification (ASJC) codes

  • Genetics
  • General

Cite this

Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. / 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.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 44, 01.11.2005, p. 16096-16101.

Research output: Contribution to journalArticle

Takayanagi, Y, Yoshida, M, Bielsky, IF, Ross, HE, Kawamata, M, Onaka, T, Yanagisawa, T, Kimura, T, Matzuk, MM, Young, LJ & Nishimori, K 2005, 'Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice', Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 44, pp. 16096-16101. https://doi.org/10.1073/pnas.0505312102
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. / Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 44. pp. 16096-16101.
@article{cc70cbdd50c14dc2bc93376131d50ebb,
title = "Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice",
abstract = "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 Oxtr-/- 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.",
author = "Yuki Takayanagi and Masahide Yoshida and Bielsky, {Isadora F.} and Ross, {Heather E.} and Masaki Kawamata and Tatsushi Onaka and Teruyuki Yanagisawa and Tadashi Kimura and Matzuk, {Martin M.} and Young, {Larry J.} and Katsuhiko Nishimori",
year = "2005",
month = "11",
day = "1",
doi = "10.1073/pnas.0505312102",
language = "English",
volume = "102",
pages = "16096--16101",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "44",

}

TY - JOUR

T1 - Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice

AU - Takayanagi, Yuki

AU - Yoshida, Masahide

AU - Bielsky, Isadora F.

AU - Ross, Heather E.

AU - Kawamata, Masaki

AU - Onaka, Tatsushi

AU - Yanagisawa, Teruyuki

AU - Kimura, Tadashi

AU - Matzuk, Martin M.

AU - Young, Larry J.

AU - Nishimori, Katsuhiko

PY - 2005/11/1

Y1 - 2005/11/1

N2 - 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 Oxtr-/- 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.

AB - 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 Oxtr-/- 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.

UR - http://www.scopus.com/inward/record.url?scp=27644476955&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27644476955&partnerID=8YFLogxK

U2 - 10.1073/pnas.0505312102

DO - 10.1073/pnas.0505312102

M3 - Article

VL - 102

SP - 16096

EP - 16101

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 44

ER -