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Gene Regulation and Epigenetics

開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

CTCF is an important factor for normal neuronal distribution, generation and development in inhibitory neurons

  • P3-034
  • 谷垣 宏美 / Hiromi Tanigaki:1 八木 健 / Takeshi Yagi:1,4 木津川 尚史 / Takeshi Kitsukawa:1,4 平山 晃斉 / Teruyoshi Hirayama:1,4 澁木 克栄 / Katsuei Shibuki:2,4 吉武 講平 / Kouhei Yoshitake:2,4 Niels Galjart / Galjart Niels:3 
  • 1:大阪大院生命機能 時空生物学講座 / Grad. Sch. of Front. Biosci., Osaka Univ., Osaka, Japan 2:新潟大学 脳研究所 システム脳生理学分野 / Dept. of Neurophysiol., Brain Res. Inst., Niigata Univ., Niigata, Japan 3:Dept. of Cell Biol. and Gen., Erasmus MC., Rotterdam, The Netherlands / Dept. of Cell Biol. and Gen., Erasmus MC., Rotterdam, The Netherlands 4:JST-CREST, Tokyo, Japan / JST-CREST, Suita, Japan 

CTCF (CCCTC-binding factor) and cohesin are playing an important role in chromatin architectures, and regulate gene expressions. Mutation in cohesion-related genes has been reported as the cause of Cornelia de Lange syndrome with mental retardation. On the other hand, CTCF knockout mice show early embryonic lethality, so it presumed that the mutations of the human CTCF gene lead to lethality. Recently reported that de novo mutations in the CTCF caused symptom such as intellectual disability and developmental delay. These results imply that the mutations of CTCF in a neuronal cell lineage lead to the disorder of nervous system. A balance between excitatory and inhibitory neurons needs to develop functional neuronal networks. In this research, we generated inhibitory neuron-specific CTCF conditional knockout mice (cKO) by expressing Cre in the downstream of Gad67 promoter, and analyzed. CTCF-cKO mice were born at the expected Mendelian ratio, but 68% of CTCF-cKO mice died within 1 day after birth. Subsequently, they gradually died and all of the CTCF-cKO mice died within 18 days after birth. The CTCF-cKO mice showed abnormal behavior, like epileptic seizures. In addition, CTCF-cKO mice showed obvious growth retardation compared with control littermates at postnatal day 14. We observed distributions of inhibitory neurons by using immunohistochemistry method and found the abnormal distribution in the hippocampus and cortex of CTCF-cKO mice. Next, we stimulated mice's whiskers at P14 and imaging neural activity by detecting intrinsic fluorescence of flavin protein in the somatosensory cortex. The control mice group showed the activity only the region which correspond to stimulated whiskers, whereas CTCF-cKO mice group showed the activity not only correspond to stimulated whiskers but also wide cortical area. These results suggested the deletion of CTCF in inhibitory neurons has influence on their distribution pattern, and that block normal neural activity.

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