Deficiency of Serotonin in Raphe Neurons and Altered Behavioral Responses in Tryptophan Hydroxylase 2-Knockout Medaka (Oryzias latipes)

Zebrafish. 2017 Dec;14(6):495-507. doi: 10.1089/zeb.2017.1452. Epub 2017 Sep 21.


Serotonin (5-hydroxytryptamine [5-HT]) is a bioactive monoamine that acts as a neurotransmitter in the central and peripheral nervous system of animals. Teleost fish species have serotonergic neurons in the raphe nuclei of the brainstem; however, the role of 5-HT in the raphe neurons in teleost fish remains largely unknown. Here, we established a medaka (Oryzias latipes) strain with targeted disruption of tryptophan hydroxylase 2 (tph2) gene that is involved in the 5-HT synthesis in the raphe nuclei. Immunohistochemistry and mass spectrometry analysis revealed that the homozygous mutants (tph2Δ13/Δ13) lacked the ability to synthesize 5-HT in the raphe neurons. To investigate the effects of 5-HT deficiency in adult behaviors, the mutant fish were subjected to five behavioral paradigms (diving, open-field, light-dark transition, mirror-biting, and two-fish social interaction). The homozygous mutation caused a longer duration of freezing response in all examined paradigms and reduced the number of entries to the top area in the diving test. In addition, the mutants exhibited a decreased number of mirror-biting in the males and an increased contact time in direct social interaction between the females. These results indicate that this tph2-knockout medaka serves as a good model to analyze the effects of 5-HT deficiency in the raphe neurons.

Keywords: behavior; knockout; medaka; serotonin; tryptophan hydroxylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified / genetics*
  • Animals, Genetically Modified / growth & development
  • Animals, Genetically Modified / metabolism
  • Behavior, Animal
  • Female
  • Male
  • Neurons / metabolism*
  • Oryzias / genetics*
  • Oryzias / growth & development
  • Oryzias / metabolism
  • Raphe Nuclei / metabolism*
  • Serotonin / deficiency*
  • Tryptophan Hydroxylase / physiology*


  • Serotonin
  • Tryptophan Hydroxylase