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Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities

Molecular Psychiatry volume 15, pages 177–184 (2010)Cite this article

Abstract

Mutations in SLITRK1 are found in patients with Tourette's syndrome and trichotillomania. SLITRK1 encodes a transmembrane protein containing leucine-rich repeats that is produced predominantly in the nervous system. However, the role of this protein is largely unknown, except that it can modulate neurite outgrowth in vitro. To clarify the role of Slitrk1 in vivo, we developed Slitrk1-knockout mice and analyzed their behavioral and neurochemical phenotypes. Slitrk1-deficient mice exhibited elevated anxiety-like behavior in the elevated plus-maze test as well as increased immobility time in forced swimming and tail suspension tests. Neurochemical analysis revealed that Slitrk1-knockout mice had increased levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol. Administration of clonidine, an α2-adrenergic agonist that is frequently used to treat patients with Tourette's syndrome, attenuated the anxiety-like behavior of Slitrk1-deficient mice in the elevated plus-maze test. These results lead us to conclude that noradrenergic mechanisms are involved in the behavioral abnormalities of Slitrk1-deficient mice. Elevated anxiety due to Slitrk1 dysfunction may contribute to the pathogenesis of neuropsychiatric diseases such as Tourette's syndrome and trichotillomania.

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Acknowledgements

We thank Dr Tadafumi Kato and Dr Takeo Yoshikawa (RIKEN BSI) for their critical comments on the paper, Dr Mika Tanaka and Ms Chieko Nishioka for their assistance in generating Slitrk1-knockout mice, Ms Chihiro Homma for her assistance in behavioral analysis and Mr Masaki Kumai (Support Unit for Animal Experiments, RIKEN BSI) for his help in generating the anti-Slitrk1 antibody. This study was supported by RIKEN BSI funds and the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Laboratory for Behavioral and Developmental Disorders, RIKEN Brain Science Institute, Wako-shi, Saitama, Japan

    K Katayama, T Inoue, M Ota & J Aruga

  2. Support Unit for Animal Experiments, RIKEN Brain Science Institute, Wako-shi, Saitama, Japan

    K Yamada

  3. Neuronal Circuit Mechanisms Research Group, RIKEN Brain Science Institute, Wako-shi, Saitama, Japan

    V G Ornthanalai & N P Murphy

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  1. K Katayama
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Correspondence to J Aruga.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Katayama, K., Yamada, K., Ornthanalai, V. et al. Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities. Mol Psychiatry 15, 177–184 (2010). https://doi.org/10.1038/mp.2008.97

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