A production of animal model for neurofibrillary tangles of Alzheimer's disease

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08680806
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tohoku University
• Principal Investigator: SHIN Ryoung-Woon Tohoku University Lecturer, 医学部, 講師 (40271910)
• Co-Investigator(Kenkyū-buntansha): KITAMOTO Tetsuyuki Tohoku University Professer, 医学部, 教授 (20192560)
• Project Period (FY): 1996 – 1997
• Keywords: Alzheimer's disease / neurofibrillary tangles / tau / PHFtau

Research Abstract

A production of animal model for neurofibriallay tangles of Alzheimer's disease
Neurofibrillary tangles (NFTs) are one of the main pathological lesions of the brains affected with Alzheimer's disease (AD) and are considered to be closely associated with neuronal loss and its clinical manifestation dementia.
The mechanisms involved in the formation and deposition of highly phosphorylated tau (PHFtau) which constitutes NETs should therefor be clarified for the insights into the pathogenesis of AD.In this study we aimed at producing transgenic mice which overexpress human tau as an animal model for AD NFTs. A construct in which cDNA of human tau and that for tau protein kinase I linked in tandem by CITE DNA were placed under the control of CMV-IE enhancer/beta-actin promoter was used to generate the transgenic mice. In these transgenic mice Nothern blot and immunohistochemistry revealed that the expression of human tau was at the same level or under the level of endogenous mouse tau. The construct used proved not suitable for the overexpression of tau in the CNS of the transgenic mice. We then turned to use mouse prion gene promoter, which was shown to overexptess transgene for human prion. This time we put a target for human presenilin 1, arecently identified gene associated with familial Alzheimer's disease. Using a construct in which cDNA of human presenilin 1 was placed under the control of the mouse prion gene promoter we succeeded in making transgenic mice which overexpress human PS1.
Based on this system we will produce transgenic mice which overexpress human tau as the animal model of AD NFTs.

Research Products

• [Publications] Shin R-W, Ogion K, Kondo A, Saido TC, Trojanowski JQ, Kitamoto T, Tateishi J.: "Amyloid β-protein(Aβ)1-40 but not Aβ1-42 contributes to the experimental formation of Alzheimer disease amyloisd fibrils in rat brain." J Neurosci. 17. 8187-8193 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shin R-W.: "Interaction of aluminum with paired helical filament τ is involved in neurofibrillary pathology of Alzheimer's disease" Gerontology. 46. 16-23 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Iino K, Sasano H, Oki Y, Andoh N, Shin R-W, Kitamoto T, Totsune K, Takahashi K, Suzuki H, Nagura H, Yoshimi T.: "Urocortin expression in human pituitary gland and pituiatry adenoma." J Clin Endocrinol Metab. 82. 3842-3850 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shin R-W,Ogino K,Kondo A,Saido TC,Trojanowski JQ,Kitamoto T,Tateishi J.: "Amyloid beta-protein (Abeta) 1-40 but not Abeta1-42 contributes to the experimental formation of Alzheimer disease amyloid fibrils in rat brain." J Neurosci. 17. 8187-8193 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Shin R-W.: "Interaction of aluminum with paired helical filament tau is involved in neurofibrillary pathology of Alzheimer's disease" Gerontology. 46. 16-23 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Iino K,Sasano H,Oki Y,Andoh N,Shin R-W,Kitamoto T,Totsune K,Takahashi K,Suzuki H,Nagura H,Yoshimi T.: "Urocortin expression in human pituitary gland and pituitary adenoma." J Clin Endocrinol Metab. 82. 3842-3850 (1997)
  • Description: 「研究成果報告書概要(欧文)」より