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Norway

PMID:29339520  

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

Jung-Hwa Choi | Yun-Mi Jeong | Sujin Kim | Boyoung Lee | Krishan 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
Proceedings of the National Academy of Sciences of the United States of America | 2018

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.

Pubmed ID: 29339520

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DECIPHER (tool)

RRID:SCR_006552

Interactive database which incorporates a suite of tools designed to aid the interpretation of submicroscopic chromosomal imbalance. Used to enhance clinical diagnosis by retrieving information from bioinformatics resources relevant to the imbalance found in the patient. Contributing to the DECIPHER database is a Consortium, comprising an international community of academic departments of clinical genetics. Each center maintains control of its own patient data (which are password protected within the center''''s own DECIPHER project) until patient consent is given to allow anonymous genomic and phenotypic data to become freely viewable within Ensembl and other genome browsers. Once data are shared, consortium members are able to gain access to the patient report and contact each other to discuss patients of mutual interest, thus facilitating the delineation of new microdeletion and microduplication syndromes.

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