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Anxiety Disorders

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

bronx waltzerマウス変異遺伝子Srrm4の脳内発現とGABAergic interneuronへの影響
Brain expression pattern of Srrm4, the gene mutated in bronx waltzer mice, and its effect on GABAergic interneuron

  • P2-341
  • 白川 由佳 / Yuka Shirakawa:1 泉 仁美 / Hitomi Izumi:1 中村 祥子 / Shoko Nakamura:2 井上 健 / Ken Inoue:2 後藤 雄一 / Yu-ichi Goto:2 稲垣 真澄 / Masumi Inagaki:1 
  • 1:国立精神・神経医療研究センター 精神保健研究所 知的障害研究部 / National Institute of Mental Health, NCNP, Tokyo, Japan 2:国立精神・神経医療研究センター 神経研究所 疾病研究第二部 / National Institute of Neuroscience, NCNP, Tokyo, Japan 

The homozygous bronx waltzer (bv) mouse is a model of hearing impairment with selective inner hair and pillar cell damage in the cochlea occurring early postnatal period. Recently, a splicing factor-encoding gene Ser/Arg repetitive matrix 4 (Srrm4) was found as a gene for bv mice, and it was suggested that the defective Srrm4-dependent alternative splicing results in degeneration of the inner hair cell. We also found that the bv mice exhibit high levels of anxiety accompanied by a reduction of parvalbumin (PV)-positive GABAergic interneurons in the anterior cingulated, somatosensory and auditory cortices at postnatal day (P) 56. However, the function of Srrm4 in the central nervous system (CNS) has yet to be determined. In the present study, we examine the expression pattern of Srrm4 mRNA in CNS by in situ hybridization (ISH). The ISH in wild-type mouse brains at P1, P7 and P21 demonstrated that Srrm4 mRNA is intensely expressed in the hippocampus, olfactory bulb and cerebellum, especially in the layers predominated by excitable neurons. In the cortex Srrm4 is widely and diffusely expressed throughout the cortical layers. Next, we examined the number of PV-positive GABAergic interneurons in the bv cortex by immunohistochemistry at P20-22. We observed no difference in anterior cingulate, somatosensory, visual and auditory cortices in comparison with wild-type. These results suggest that Srrm4 is predominantly expressed in the excitable neurons rather than interneuron, and the reduction of PV-containing GABAergic interneuron in bv mice is likely a postnatal event, possibly in the neuronal maturation rather than developmental aberration. We thus speculate that the Srrm4 mutation indirectly affects the maturation of interneuron in the CNS. Further study is necessary to illuminate the role of Srrm4 in the maturation of GABAergic interneuron.

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