Searching for new treatment of Hirschspurung disease by using newly developed mice model

• Project/Area Number: 23792033
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: Juntendo University
• Principal Investigator: TANAKA Nana 順天堂大学, 医学部, 助教 (50530656)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ヒルシュスプルング病 / 神経堤細胞 / マウスモデル / 蛍光イメージング / 腸管神経系 / 細胞外マトリックス / ラミニン / 動物モデル / 仙骨神経堤細胞 / Sox10 / 器官培養 / 疾患モデルマウス / animal model / 神経提細胞 / ライブイメージング / SOX10

Research Abstract

Disruption of vagal enteric neural crest cells(NCC) migration appears to induce sacral NCC activation in the anorectum, which could have implications for the etiology of the thick nerve fibers seen in Hirschsprung disease(HD) anorectum, which could in fact be a secondary phenomenon.
To establish new treatment for HD, we examined the effect of laminin-1 in NCC migration using SOX10-Venus mice gut. Our results suggest that laminin promotes NCC migration in mice.

Research Products

• [Journal Article] Abnormal neural crest innervation in Sox10-Venus mice with all-trans retinoic acid-induced anorectal malformations. (2014)
  • Author(s): Suzuki R, Miyahara K, Murakami H, Doi T, Lane GJ, Mabuchi Y, Suzuki N, Yamataka A, Akazawa C.
  • Journal Title: Pediatric Surgery International Volume: Feb;30(2) Issue: 2 Pages: 189-95
  • DOI: 10.1007/s00383-013-3452-z
  • Peer Reviewed
• [Journal Article] Laminin-1 promotes enteric nervous system development in mouse embryo (2013)
  • Author(s): Nakazawa N, Miyahara K, Okawada M, Yamataka A, Suzuki R, Akazawa C, Tomikawa-Ichikawa N, Arikawa-Hirasawa E
  • Journal Title: Pediatr Surg Int Volume: 29(11) Pages: 1205-1208
• [Journal Article] Anorectal neural crest derived cell behavior after the migration of vagal neural crest derived cells is surgically disrupted : implications for the etiology of Hirschsprung's disease (2013)
  • Author(s): Miyahara K, Kato Y, Suzuki R, Akazawa C, Tanaka N, Koga H, Doi T, Lane GJ, Yamataka A
  • Journal Title: Pediatr Surg Int Volume: 29(1) Pages: 9-12
• [Journal Article] Laminin-1 promotes enteric nervous system development in mouse embryo. (2013)
  • Author(s): Nakazawa N, Miyahara K, Okawada M, Yamataka A, Suzuki R, Akazawa C, Tomikawa-Ichikawa N, Arikawa-Hirasawa E.
  • Journal Title: Pediatric Surgery International Volume: Nov;29(11) Issue: 11 Pages: 1205-8
  • DOI: 10.1007/s00383-013-3388-3
  • Peer Reviewed
• [Journal Article] Anorectal neural crest derived cell behavior after the migration of vagal neural crest derived cells is surgically disrupted: implications for the etiology of Hirschsprung's disease. (2013)
  • Author(s): Miyahara K, Kato Y, Suzuki R, Akazawa C, Tanaka N, Koga H, Doi T, Lane GJ, Yamataka A.
  • Journal Title: Pediatric surgery international Volume: Jan;29(1) Issue: 1 Pages: 9-12
  • DOI: 10.1007/s00383-012-3201-8
  • Peer Reviewed
• [Journal Article] Visualization of enteric neural crest cell migration in SOX10 transgenic mouse gut using time-lapse fluorescence imaging. (2011)
  • Author(s): Miyahara K, Kato Y, Koga H, et al.
  • Journal Title: Journal of Pediatric Surgery Volume: 46 Pages: 2305-8
  • Peer Reviewed
• [Presentation] 神経堤細胞イメージングマウスを用いたレチノイン酸誘導直腸肛門奇形マウスの病態解析 (2014)
  • Author(s): 宮原 克、鈴木亮太、村上 寛、土井 崇、山高篤行、赤澤智宏
  • Organizer: 第51回日本小児外科学会
  • Place of Presentation: 大阪
• [Presentation] Laminin-1 promotes neuronal development in mouse embryonic gut (2013)
  • Author(s): N Nakazawa, K Miyahara, M Okawada, R Suzuki, M Urao, C Akazawa, A Yamataka, E Arikawa-Hirasawa
  • Organizer: 第50回日本小児外科学会
  • Place of Presentation: 東京
• [Presentation] ABNORMAL ENTERIC INNERVATION OF THE RECTUM IN SOX10-VENUS MICE WITH RETINOIC ACID INDUCED ANORECTAL MALFORMATION. (2013)
  • Author(s): R. Suzuki, K. Miyahara, Y. Mabuchi, N. Suzuki, H. Murakami, G.J. Lane, C. Akazawa, A. Yamataka
  • Organizer: 26th International Symposium of Pediatric Surgical Research
  • Place of Presentation: Cape Town、South Africa
• [Presentation] Laminin-1 promotes neuronal development in mouse embryonic gut. (2013)
  • Author(s): N Nakazawa, K Miyahara, M Okawada, R Suzuki, M Urao, C Akazawa, A Yamataka, E Arikawa-Hirasawa
  • Organizer: 第50回日本小児外科学会
  • Place of Presentation: 東京
• [Presentation] Anorectal neural crest derived cell behavior after the migration of vagal neural crest derived cells is surgically disrupted : Implications for the etiology of Hirschsprung's disease (2012)
  • Author(s): N Nakazawa, K Miyahara, R Suzuki, Y Kato, GJ Lane, C Akazawa, H Koga, T Doi, A Yamataka
  • Organizer: 25th International symposium on paediaric surgical research
  • Place of Presentation: London, UK
• [Presentation] Laminin-1 promotes neuronal development in mouse embryonic gut (2012)
  • Author(s): N Nakazawa, K Miyahara, M Okawada, Y Liu, C Akazawa, A Yamataka, E Arikawa-Hirasawa
  • Organizer: 25th International symposium on paediaric surgical research
  • Place of Presentation: London, UK
• [Presentation] ANORECTAL NEURAL CREST DERIVED CELL BEHAVIOR AFTER THE MIGRATION OF VAGAL NEURAL CREST DERIVED CELLS IS SURGICALLY DISRUPTED: IMPLICATIONS FOR THE ETIOLOGY OF HIRSCHSPRUNG’S DISEASE (2012)
  • Author(s): N Nakazawa, K Miyahara, R Suzuki, Y Kato, GJ Lane, C Akazawa, H Koga, T Doi, A Yamataka
  • Organizer: XXVth International symposium on paediatric surgical reserch
  • Place of Presentation: London,UK
• [Presentation] LAMININ-1 PROMOTES NEURONAL DEVELOPMENT IN MOUSE EMBRYONIC GUT (2012)
  • Author(s): N Nakazawa, K Miyahara, M Okawada, Y Liu, C Akazawa, A Yamataka, E Arikawa-Hirasawa
  • Organizer: XXVth International symposium on paediatric surgical reserch
  • Place of Presentation: London,UK
• [Presentation] FLUORESCENT STAINING OF SOX10 AS A MARKER OF INTESTINAL ISCHEMIA (2012)
  • Author(s): T Takahashi, M Okawada, K Miyahara, M Takeda, GJ Lane, C Akazawa, A Yamataka
  • Organizer: XXVth International symposium on paediatric surgical reserch
  • Place of Presentation: London,UK
• [Presentation] 蛍光ライブイメージング法を用いたSOX10-VENUS トランスジェニックマウスの腸管神経系形成過程の観察 (2011)
  • Author(s): 宮原 克、加藤善史、古賀寛之、鈴木亮太、赤澤智宏、山高篤行
  • Organizer: 日本小児外科学会
  • Place of Presentation: 東京
• [Presentation] Hirschsprung病に関する神経提細胞イメージングモデルマウスの開発 (2011)
  • Author(s): 宮原 克、加藤善史、古賀寛之、赤澤智宏、山高篤行
  • Organizer: 日本小児外科学会
  • Place of Presentation: 東京
• [Remarks] Aesculap Prize (Second Prize) at the 25^<th> International Symposium of Paediatric Surgical Research, London, UK, 2012