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MOLECULAR BIOLOGICAL STUDY ON PATHOGENESIS IN MURINE EMBRYOS WITH AN ORECTAL MALFORMATIONS

Research Project

Project/Area Number 11671774
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatric surgery
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

TOKIWA Kazuaki  KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (30163968)

Co-Investigator(Kenkyū-buntansha) IWAI Naomi  KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, PROFESSOR, 医学部, 教授 (90128695)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsANORECTAL MALFORMATIONS / MURINE MODELE / MBRYOLOGY / CELL PROLIFERATION / MOLECULAR BIOLOGY / APOPTOSIS
Research Abstract

The pathogenesis of anorectal malformations (ARM) remains unclear, although several possible causative factors have been suggested using model animals from mutant strains, or induced by teratogenic agents. In this study, we examined the proliferation and programmed death (apoptosis) of cells forming the urogenitorectal region to clarify the mechanism of pathogenesis in murine models with ARM induced by etretinate, with special reference to molecular biology.
Pregnant mice were fed 60 mg/kg of etretinate on the ninth gestation day (E9).Embryos were obtained between E9.5 and E13, and prepared for histological study. Cell proliferation was examined using proliferative cell-specific nuclear antigen (PCNA) expression. Apoptosis was identified by detecting in situ DNA fragmentation using the TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method.
Over 95 % of etretinate-treated embryos had ARM including rectoprostatic urethral or rectocloacal fistula. In the histological study, ARM embryos showed defective cell proliferation in the cloacal membrane and excessive apoptosis in the dorsocaudal region on E11, which resulted in a lack of apoptosis in the anal orifice and a short tail on E12, respectively. Cells forming the urorectal septum showed the same pattern of cell proliferation and apoptosis both in ARM embryos and the controls.
These results suggest that impairments of embryonal cellular dynamics in the cloacal membrane and dorsocaudal region induce some types of ARM.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report

Research Products

(33 results)

All Other

All Publications (33 results)

  • [Publications] Imazu M: "Factor of biliary carcinogenesis in choledochal cysts"European Journal of Pediatric Surgery. 11. 24-27 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamagami T: "Intrahepatic portosystemic venous shunt associated with biliary atresia"Pediatric Radiology. 30. 489-491 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kubota Y: "Congenital anomalies in mice induced by etretinate"European Journal of Pediatric Surgery. 10. 248-251 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tokiwa K: "Mucosal cell proliferation activity of the gallbladder in chilche with anomalous arrangement of the pancreaticobiliary duct"Journal of Hepato-biliary Pancreatic Surgery. 6. 213-217 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuwabara M: "Endosonographic study of anal sphincters in patients after surgery for Hirschspruag's disease"European Journal of Pediatric Surgery. 34. 450-453 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kubota Y: "Development of anorectal malformations using etretinate"European Journal of Pediatric Surgery. 33. 127-129 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] ImazuM., Iwai N., Tokiwa K., Shimotake T., Kimura O., Ono S.: "Factors of biliary carcinogenesis in choledochal cysts"Eur J Pediatr Surg. 11. 24-27 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomiyama H, Shimotake T, Ono S, Kimura O, Tokiwa K, Iwai N: "Relationship between the type of RET/GDNF/NTN or SOX10 gene mutations and long-term results after surgery for total colonic aganglionosis with small bowel involvement"J Pediatr Surg. 36. 1685-1688 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ono S., Tokiwa K., Aoi S., N Iwai., Nakanoin H.: "A bleeding tendency as the first symptom of a choledochal cyst"Pediatr Surg Int. 16. 111-112 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Go S., Tokiwa K., Imazu M., Higuchi K., Iwai N.: "Arteriovenous malformation of the penis in an infant"J Pediatr Surg. 35. 1130-1131 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamagami T., Nakamura T., Tokiwa K., Ohno K., Itoh H., Maeda T.: "Intrahepatic portosystemic venous shunt associated with biliary atresia"Pediatr Radiol. 30. 489-491 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kubota Y., Shimotake T., Iwai N.: "Congenital anomalies in mice induced by etretinate"Eur J Pediatr Surg. 10. 248-251 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tokiwa K., Ono S., Iwai N.: "Mucosal cell proliferation activity of the gallbladder in children with anomalous arrangement of the pancreaticobiliary duct"J Hep Bil Pancr Surg. 6. 213-217 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ono S., Tokiwa K., Iwai N.: "Cellular activity in the gallbladder of children with anomalous arrangement of the pancreaticobiliary duct"J Pediatr Surg. 34. 962-966 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuwahara M., Iwai N., Yanagihara J., Tokiwa K., Fukata R.: "Endosonographic study of anal sphincters in patients after surgery for Hirschsprung' s disease"J Pediatr Surg. 34. 450-453 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Inoue K., Shimotake T., Inoue K., Tokiwa K., Iwai N.: "Mutational analysis of the RET proto-oncogene in a kindred with multiple endocrine neoplasia type 2A and Hirschsprung' s disease"J Pediatr Surg. 34. 1552-1554 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kubota Y., Shimotake T., Yanagihara J., Iwai N.: "Development of anorectal malformations using etretinate"J Pediatr Surg. 33. 127-129 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Imazu M: "Factors of bilsary carcinogenesis in chsledochsl cycts"European Journal of Pediatric Surgery. 11. 24-27 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomiyama H: "Relationship between the type of RET/GDNF/NTN or SOX/O gene mutations and long-tern results after for total colonic aganglionosis with small howel involvement"European Journal of Pediatric Surgery. 36. 1685-1688 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ono S: "A bleeding tendency as first symptom of a cheledochal cyst"Pedoatroc Surgery International. 16. 111-112 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamagami T: "Intrahepatic portosystemic venous shunt associated with biliary atresia"Pedoatroc Radiolosy. 30. 489-491 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Go S: "Arterio venous malformation of the penis in an infant"Journal of Pediatric Surgery. 35. 1130-1131 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kubota Y: "Congenital anomalies in mice induced by etretinate"European Jonrnal of Pediatric Surgery. 10. 248-251 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tokiwa K: "Mucosal cell proliferation activity of the gallbladder in children with anomalous arrangement of the Pancreaticobiliary duct"Journal of Hepats-Biliary Panosealic Surgesy. 6. 213-217 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Inone K: "Mutational analysis of the RET proto-oncogene in akindred with multiple endocrine heoplasia type 2A and Hirschsprung's disease"Journal of Pediatric Surgery. 34・10. 1552-1554 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ono S: "Cellular activity in the gallbladder of children with anomalous arrangement of the pancreaticobiliary duct"Journal of Pediatric Surgery. 34・6. 962-966 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kuwahara M: "Endosographic study of anal sphincters in patients after swigery for Hirschsprung's disease"Journal of Pediatric Surgery. 34・3. 450-453 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kubata Y: "Development of anorectal malformations using etretinate"Journal of Pediatric Surgesy. 33・1. 127-129 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tokiwa K: "Mucosal cell proliferation activity of the gallbladder is children with anomalous arrangement of the pancreaticobiliary duct"Journal of Hepato-Biliary Pancreatic Surgerg. 6. 213-217 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Inoue K: "Mutatinal analysis of the RET proto-oncogene in a kindred with multiple endocrine neoplasia type 2A and Hirschsprung's disease"Journal of Pediatric Surgery. 34・10. 1552-1554 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ono S: "Cellular activity in the gallbladder of children with anomalous arrangement of the pancreaticobiliary duct"Journal of Pediatric Surgery. 34・6. 962-966 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kumahara M: "Endosonographic study of anal sphincters in patients after surgery for Hirschspring's disease"Journal of Pediatric Surgery. 34・3. 450-453 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kubota Y: "Development of anorectal malformations using etretinate"Journal of Pediatric Surgery. 33・1. 127-129 (1998)

    • Related Report
      1999 Annual Research Report

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Published: 1999-03-31   Modified: 2016-04-21  

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