Targeted knockout of a chemokine-like gene increases anxiety and fear responses

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Title
Targeted knockout of a chemokine-like gene increases anxiety and fear responses
Author(s)
Jung-Hwa Choi; Yun-Mi Jeong; Sujin Kim; Boyoung Lee; Kirishan Ariyasiri; Hyun-Taek Kim; Seung-Hyun Jung; Kyu-Seok Hwang; Tae-IK Choi; Chul O Park; Won-Ki Huh; Matthias Carl; Jill A. Rosenfeld; Salmo Raskin; Alan Ma; Jozef Gecz; Hyung-Goo Kim; Jin-Soo Kim; Ho-Chul Shin; Doo-Sang Park; Robert Gerlai; Bradley B. Jamieson; Joon S. Kim; Karl J. Iremonger; Sang H. Lee; Hee-Sup Shin; Cheol-Hee Kim
Publication Date
2018-01
Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.115, no.5, pp.E1041 - E1050
Publisher
NATL ACAD SCIENCES
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
URI
https://pr.ibs.re.kr/handle/8788114/4391
ISSN
0027-8424
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > Journal Papers (저널논문)
Center for Cognition and Sociality(인지 및 사회성 연구단) > Journal Papers (저널논문)
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