한빛사 논문
Jung-Hwa Choia,1, Yun-Mi Jeonga,1, Sujin Kimb,c, Boyoung Leec, Krishan Ariyasiria, Hyun-Taek Kima, Seung-Hyun Junga, Kyu-Seok Hwanga, Tae-Ik Choia, Chul O Parkd, Won-Ki Huhd, Matthias Carle, Jill A. Rosenfeldf, Salmo Rasking, Alan Mah,i, Jozef Geczj,k, Hyung-Goo Kiml,m, Jin-Soo Kimn,o, Ho-Chul Shinp, Doo-Sang Parkp, Robert Gerlaiq, Bradley B. Jamiesonr,s, Joon S. Kimr,s, Karl J. Iremongerr,s, Sang H. Leet, Hee-Sup Shinb,c,2, and Cheol-Hee Kima,2
aDepartment of Biology, Chungnam National University, 34134 Daejeon, South Korea;
bInstitute for Basic Science School, University of Science and Technology, 34113 Daejeon, South Korea;
cCenter for Cognition and Sociality, Institute for Basic Science, 34141 Daejeon, South Korea;
dDepartment of Biological Sciences, Seoul National University, 151-747 Seoul, South Korea;
eLaboratory of Translational Neurogenetics, Center for Integrative Biology, University of Trento, 38123 Trento, Italy;
fDepartment of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX 77030;
gGroup for Advanced Molecular Investigation, Health and Biosciences School, Pontifícia Universidade Católica do Paraná, 80215-901 Curitiba Paraná, Brazil;
hDepartment of Genetics, Nepean Hospital Sydney, University of Sydney, NSW 2006, Australia;
iDiscipline of Child & Adolescent Health, Children’s Hospital at Westmead Clinical School, University of Sydney, NSW 2006, Australia;
jSchool of Medicine and The Robinson Research Institute, University of Adelaide, Adelaide 5000, Australia;
kHealthy Mothers and Babies, South Australian Health and Medical Research Institute, Adelaide 5000, Australia;
lDepartment of OB/GYN, Augusta University, Augusta, GA 30912;
mDepartment of Neuroscience and Regenerative Medicine, Augusta University, Augusta, GA 30912;
nCenter for Genome Engineering, Institute for Basic Science, Seoul National University, 151-747 Seoul, South Korea;
oDepartment of Chemistry, Seoul National University, 151-747 Seoul, South Korea;
pKorea Research Institute of Bioscience and Biotechnology, 305-806 Daejeon, South Korea;
qDepartment of Psychology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada;
rDepartment of Physiology, University of Otago, 9054 Dunedin, New Zealand;
sCentre for Neuroendocrinology, University of Otago, 9054 Dunedin, New Zealand;
tDepartment of Pharmacology & Toxicology, Neuroscience Research Institute, Medical College of Wisconsin, WI 53226
Footnotes
1J.-H.C. and Y.-M.J. contributed equally to this work.
2To whom correspondence may be addressed.
Abstract
Emotional responses, such as fear and anxiety, are fundamentally important behavioral phenomena with strong fitness components in most animal species. Anxiety-related disorders continue to represent a major unmet medical need in our society, mostly because we still do not fully understand the mechanisms of these diseases. Animal models may speed up discovery of these mechanisms. The zebrafish is a highly promising model organism in this field. Here, we report the identification of a chemokine-like gene family, samdori (sam), and present functional characterization of one of its members, sam2. We show exclusive mRNA expression of sam2 in the CNS, predominantly in the dorsal habenula, telencephalon, and hypothalamus. We found knockout (KO) zebrafish to exhibit altered anxiety-related responses in the tank, scototaxis and shoaling assays, and increased crh mRNA expression in their hypothalamus compared with wild-type fish. To investigate generalizability of our findings to mammals, we developed a Sam2 KO mouse and compared it to wild-type littermates. Consistent with zebrafish findings, homozygous KO mice exhibited signs of elevated anxiety. We also found bath application of purified SAM2 protein to increase inhibitory postsynaptic transmission onto CRH neurons of the paraventricular nucleus. Finally, we identified a human homolog of SAM2, and were able to refine a candidate gene region encompassing SAM2, among 21 annotated genes, which is associated with intellectual disability and autism spectrum disorder in the 12q14.1 deletion syndrome. Taken together, these results suggest a crucial and evolutionarily conserved role of sam2 in regulating mechanisms associated with anxiety.
chemokine-like, anxiety, fear, knockout, zebrafish
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