PLoS ONE (Jan 2011)

A single amino acid mutation in SNAP-25 induces anxiety-related behavior in mouse.

  • Masakazu Kataoka,
  • Saori Yamamori,
  • Eiji Suzuki,
  • Shigeru Watanabe,
  • Taku Sato,
  • Hitoshi Miyaoka,
  • Sadahiro Azuma,
  • Shiro Ikegami,
  • Reiko Kuwahara,
  • Rika Suzuki-Migishima,
  • Yohko Nakahara,
  • Itsuko Nihonmatsu,
  • Kaoru Inokuchi,
  • Yuko Katoh-Fukui,
  • Minesuke Yokoyama,
  • Masami Takahashi

DOI
https://doi.org/10.1371/journal.pone.0025158
Journal volume & issue
Vol. 6, no. 9
p. e25158

Abstract

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Synaptosomal-associated protein of 25 kDa (SNAP-25) is a presynaptic protein essential for neurotransmitter release. Previously, we demonstrate that protein kinase C (PKC) phosphorylates Ser(187) of SNAP-25, and enhances neurotransmitter release by recruiting secretory vesicles near to the plasma membrane. As PKC is abundant in the brain and SNAP-25 is essential for synaptic transmission, SNAP-25 phosphorylation is likely to play a crucial role in the central nervous system. We therefore generated a mutant mouse, substituting Ser(187) of SNAP-25 with Ala using "knock-in" technology. The most striking effect of the mutation was observed in their behavior. The homozygous mutant mice froze readily in response to environmental change, and showed strong anxiety-related behavior in general activity and light and dark preference tests. In addition, the mutant mice sometimes exhibited spontaneously occurring convulsive seizures. Microdialysis measurements revealed that serotonin and dopamine release were markedly reduced in amygdala. These results clearly indicate that PKC-dependent SNAP-25 phosphorylation plays a critical role in the regulation of emotional behavior as well as the suppression of epileptic seizures, and the lack of enhancement of monoamine release is one of the possible mechanisms underlying these defects.