TY - JOUR
T1 - Deficiency of serotonin in raphe neurons and altered behavioral responses in tryptophan hydroxylase 2-knockout medaka (oryzias latipes)
AU - Ansai, Satoshi
AU - Hosokawa, Hiroshi
AU - Maegawa, Shingo
AU - Naruse, Kiyoshi
AU - Washio, Youhei
AU - Sato, Kenji
AU - Kinoshita, Masato
N1 - Funding Information:
The authors thank Dr. Masatomo Tagawa for support in histological analysis and Drs. Tomonori Deguchi and Susu-mu Uji for helpful discussions. They also thank Drs. Tetsushi Sakuma and Takashi Yamamoto for pFUS_A2A and pFU-S_A2B vectors, Dr. Kazuyuki Hoshijima for the pCS2TAL3DD and pCS2TAL3RR vectors, Dr. Daniel F. Voytas for the Golden Gate TALEN and TAL Effector Kit (Addgene #1000000016), Dr. Akihiro Fujikawa for advice on micro-computed tomography imaging, and National BioR-esource Project medaka for the hatching enzyme. This work was supported by a Grant-in-Aid for Japan Society for the Promotion of Science ( JSPS) Fellows (no. 13J01682 to S.A.) and the National Institute for Basic Biology Individual Collaborative Research Project (no. 14-345 to M.K.).
Publisher Copyright:
© Copyright 2017, Mary Ann Liebert, Inc. 2017.
PY - 2017/12
Y1 - 2017/12
N2 - 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.
AB - 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.
KW - behavior
KW - knockout
KW - medaka
KW - serotonin
KW - tryptophan hydroxylase
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U2 - 10.1089/zeb.2017.1452
DO - 10.1089/zeb.2017.1452
M3 - Article
C2 - 28933662
AN - SCOPUS:85036575313
VL - 14
SP - 495
EP - 507
JO - Zebrafish
JF - Zebrafish
SN - 1545-8547
IS - 6
ER -