The role of SIP1, the causative gene for Mowat-Wilson syndrome, in structural and functional development of brain

• Project/Area Number: 26461539
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Institute for Developmental Research, Aichi Human Service Center
• Principal Investigator: Higashi Yujiro 愛知県心身障害者コロニー発達障害研究所, 周生期学部, 部長 (30181069)
• Co-Investigator(Kenkyū-buntansha): 松井 ふみ子 愛知県心身障害者コロニー発達障害研究所, 周生期学部, 研究助手 (10393133)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: モワット-ウィルソン症候群 / SIP1 遺伝子 / ZFHX1ファミリー / ZEBファミリー / ノックアウトマウス / 脳 / 精神遅滞 / SIP1 / 転写因子 / δEF1 / SIP1遺伝子 / de novo変異 / モデルマウス

Outline of Final Research Achievements

1. To make the model mouse for Mowat-Wilson syndrome, we used the conditional knockout of the SIP1 gene in male germ cells to escape the difficulty in maintaining the heterozygous SIP1 knockout mice and to mimic the de novo mutation in human. We then analyzed this model mouse if they showed the relevant phenotype in relation to the symptoms in Mowat-Wilson syndrome. 2. We made the dEF1 flox mouse and analyzed its authenticity by comparing the phenotype of the conventional homozygous knockout embryos and that of the whole body knockout derived from the flox allele combined with the CAG-cre transgene. We confirmed that the flox allele we made can be the null allele through deletion of the 6th exon flanked with LoxP sequence by cre recombinase.

Research Products

• [Int'l Joint Research] ハーバード大学(米国)
• [Int'l Joint Research] テルアビブ大学(イスラエル)
• [Int'l Joint Research] モンペリエ神経科学研究所(フランス)
• [Journal Article] Regulation of trunk neural crest delamination by δEF1 and Sip1 in the chicken embryo (2016)
  • Author(s): Yasumi, T., Inoue, M., Maruhashi, M., Kamachi, Y., Higashi, Y., Kondoh, H., Uchikawa, M.
  • Journal Title: Dev. Growth. Differ. Volume: 58 Issue: 2 Pages: 205-214
  • DOI: 10.1111/dgd.12256
  • Peer Reviewed
• [Journal Article] Sip1 regulates the generation of the inner nuclear layer retinal cell lineages in mammals. (2016)
  • Author(s): Menuchin-Lasowski Y., Oren-Giladi P., Xie Q., Ezra-Elia R., Ofri R., Peled-Hajaj S., Farhy C., Higashi Y., Van de Putte T., Kondoh H., Huylebroeck D., Cvekl A., Ashery-Padan R.
  • Journal Title: Development. 143:2829-2841 (2016) Volume: 143 Issue: 15 Pages: 829-2841
  • DOI: 10.1242/dev.136101
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic disease. (2016)
  • Author(s): Rasouly, H. M., Kumar, S., Chan, S., Pisarek-Horowitz, A., Sharma, R., Xi, Q. J., Nishizaki, Y., Higashi, Y., Salant, D. J., Maas, R. L., Lu, W.
  • Journal Title: Kidney Int. Volume: 90 Issue: 6 Pages: 1262-1273
  • DOI: 10.1016/j.kint.2016.06.037
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The Zeb1 Transcription Factor Controls the Onset of Spinal Cord Astrocyte Precursor Emigration from the Ventricular Zone (2016)
  • Author(s): Ohayon, D., Garces, A., Willy Joly, W., Soukkarieh, C., Takagi, T., Sabourin, J.-C., Eric Agius, E., Darling, D. S., De Santa Barbara, P., Higashi, Y., Stolt, C. C., Jean-Philippe Hugnot, J.-P., William D. Richardson, W. D., Patrick Carroll, P. and Pattyn, A.
  • Journal Title: Cell Reports Volume: 17 Issue: 6 Pages: 1473-1481
  • DOI: 10.1016/j.celrep.2016.10.016
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate. (2016)
  • Author(s): Wu, X., Brisefio, C. G., Grajales-Reyes, G. E., Haldar, M., Iwata, A., Kretzer, N. M., Wumesh, KC., Tussiwand, R., Higashi, Y., Murphy, T. L., and Murphy, K. M.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 113 Issue: 51 Pages: 14775-14780
  • DOI: 10.1073/pnas.1611408114
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] De novo inbred heterozygous Zeb2/Sip1 mutant mice uniquely generated by germ-line conditional knockout exhibit craniofacial, callosal and behavioral defects associated with Mowat-Wilson syndrome (2015)
  • Author(s): 51.Takagi T, Nishizaki Y, Matsui F, Wakamatsu N, Higashi Y.
  • Journal Title: Hum Mol Genet. Volume: 24 Issue: 22 Pages: 6390-6402
  • DOI: 10.1093/hmg/ddv350
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Cre-LoxPシステムを利用したdenovo変異型ヒト疾患モデルマウスの作製 (2015)
  • Author(s): 高木 豪、東 雄二郎
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-02
• [Remarks] 愛知県心身障害者コロニー発達障害研究所 【トピ ック ス】