Preparation and analysis of model mice with Parkinson's disease

2000 Fiscal Year Final Research Report Summary

• Project/Area Number: 11670654
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Tokyo Metropolitan Institute of Gerontology
• Principal Investigator: TAKAHASHI Mayumi Tokyo Metropolitan Institute of Gerontology, Department of Ultrastructure, Assistant, 超微形態部門, 研究助手 (50133632)
• Co-Investigator(Kenkyū-buntansha): 白澤 卓二 財団法人 東京都老人総合研究所, 分子遺伝学部門, 室長 (80226323)
• Project Period (FY): 1999 – 2000
• Keywords: Parkinson's disease / Model mouse / Dopaminergic neuron / Superoxide / Mn-SOD / Knockout mouse / Gene therapy / Adeno virus

Research Abstract

The generation of Parkinson's disease model mouse Reactive Oxygen Species (ROS) plays a pathological role in the development of neurodegenerative diseases including Parkinson's disease. Doperminergic system in CNS participates in the higher brains functions such as recognition, motor coordination, and memory. Neuropathologically, the doperminergic neurons are vulnerable for the ageing process of the brain where the apoptotic figures are often observed in the midbrain of aged animal brains. Clinically, the reduction in the number of doperminergic neurons leads to the symptom of Parkinson's disease such as tremor, rigidity, and motor disturbance. To address the pathogenic mechanisms of Parkinson's disease in aged population, we tried to generate a model mouse in which Mn-SOD gene, a defensive enzyme against ROS, is conditionally knocked down specifically in doperminergic neurons. For this purpose, we first generated the Mn-SOD flox mouse in which recombination signal called loxp is inserted in the genomic locus of mouse Mn-SOD gene to delete the catalytic exons by cre recombinase. By crossing with TH-Cre transgenic mice (provided by Prof. Kobayashi, Fukushima) which specifically express cre recombinase in dopaminergic neurons, Mn-SOD flox mice would inactivate Mn-SOD gene in doperminergic neurons and provide an excellent model system for Parkinson's disease.

Research Products

• [Publications] Shimizu,T. et al.: "Isoaspartate formation and neurodegeneration in Alzheimer's disease."Archives of Biochemistry and Biophysics. 381. 225-234 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nakano,H. et al.: "Targeted disruption of traf5 gene causes defects in CD40-and CD27-mediated lymphocyte activation."Proc Natl Acad Sci USA. 96. 9803-9808 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tomoda,T. et al.: "A mouse serine/threonine kinase homologous to Gelegans UNC51 functions in parallel fiber formation of cerebellar granule neurons."Neuron. 24. 833-846 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shimizu, T., Watanabe, A., Ogawara, M., Mori, H., and Shirasawa, T.: "Isoaspartate formation and neurodegeneration in Alzheimer's disease."Arch. Biochem. Biophys.. 381. 225-234 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nakano, H., Sakon, S., Koseki, H., Takemori, T., Tada, K., Matsumoto, M., Munechika, E.Sakai, T., Shirasawa, T., Akiba, H., Kobata, T., Santee, S.M., Ware, C.F., Rennert, P.D., Taniguchi, M., Yagita, H., and Okumura, K.: "Targeted disruption of traf5 gene causes defects in CD40- and CD27- mediated lymphocyte activation."Proc. Natl. Acad. Sci. USA. 96. 9803-9808 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tomoda, T., Bhatt, R.S., Kuroyanagi, H., Shirasawa, T., and Hatten, M.E.: "A mouse serine threonine kinase homologous to C.elegans UNIC51 functions in parallel fiber formation of cerebellar granule neurons."Neuron. 24. 833-846 (1999)
  • Description: 「研究成果報告書概要(欧文)」より