Cd38 gene knockout juvenile mice: A model of oxytocin signal defects in autism Cd38 Gene Knockout Juvenile Mice: A Model of Oxytocin Signal Defects in Autism

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Abstract

Oxytocin (OXT) in the hypothalamus is the biological basis of social recognition, trust, and bonding. We showed that CD38, a leukaemia cell marker, plays an important role in the hypothalamus in the process of OXT release in adult mice. Disruption of Cd38 (Cd38-/-) produced impairment of maternal behavior and male social recognition in mice, similar to the behavior observed in Oxt and OXT receptor (Oxtr) gene knockout (Oxt-/- and Oxtr-/-, respectively) mice. Locomotor activity induced by separation from the dam was higher and the number of ultrasonic vocalization (USV) calls was lower in Cd38-/- than Cd38+/+ pups. These phenotypes seemed to be caused by the high plasma OXT levels during development from neonates to 3-week-old juvenile mice. ADP-ribosyl cyclase activity was markedly lower in the knockout mice from birth, suggesting that weaning for mice is a critical time window of differentiating plasma OXT. Contribution by breastfeeding was an important exogenous source for regulating plasma OXT before weaning by the presence of OXT in milk and the dam's mammary glands. The dissimilarity of Cd38-/- infant behaviour to Oxt-/- or Oxtr-/- mice can be explained partly by this exogenous source of OXT. These results suggest that secretion of OXT into the brain in a CD38-dependent manner may play an important role in the development of social behavior, and mice with OXT signalling deficiency, including Cd38-/-, Oxt -/- and Oxtr-/- mice are good animal models for developmental disorders, such as autism. © 2011 Pharmaceutical Society of Japan.

Oxytocin (OXT) in the hypothalamus is the biological basis of social recognition, trust, and bonding. We showed that CD38, a leukaemia cell marker, plays an important role in the hypothalamus in the process of OXT release in adult mice. Disruption of <i>Cd38</i> (<i>Cd38</i><sup>−/−</sup>) produced impairment of maternal behavior and male social recognition in mice, similar to the behavior observed in <i>Oxt</i> and OXT receptor (<i>Oxtr</i>) gene knockout (<i>Oxt</i><sup>−/−</sup> and <i>Oxtr</i><sup>−/−</sup>, respectively) mice. Locomotor activity induced by separation from the dam was higher and the number of ultrasonic vocalization (USV) calls was lower in <i>Cd38</i><sup>−/−</sup> than <i>Cd38</i><sup>+/+</sup> pups. These phenotypes seemed to be caused by the high plasma OXT levels during development from neonates to 3-week-old juvenile mice. ADP-ribosyl cyclase activity was markedly lower in the knockout mice from birth, suggesting that weaning for mice is a critical time window of differentiating plasma OXT. Contribution by breastfeeding was an important exogenous source for regulating plasma OXT before weaning by the presence of OXT in milk and the dam's mammary glands. The dissimilarity of <i>Cd38</i><sup>−/−</sup> infant behaviour to <i>Oxt</i><sup>−/−</sup> or <i>Oxtr</i><sup>−/−</sup> mice can be explained partly by this exogenous source of OXT. These results suggest that secretion of OXT into the brain in a CD38-dependent manner may play an important role in the development of social behavior, and mice with OXT signalling deficiency, including <i>Cd38</i><sup>−/−</sup>, <i>Oxt</i><sup>−/−</sup> and <i>Oxtr</i><sup>−/−</sup> mice are good animal models for developmental disorders, such as autism.

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 34(9), 1369-1372, 2011

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130001872426
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • Article Type
    特集
  • ISSN
    0918-6158
  • NDL Article ID
    11217172
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-V41
  • Data Source
    NDL  IR  J-STAGE 
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