The production of newly ALS model mice

2015 Fiscal Year Final Research Report

• Project/Area Number: 24591275
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kitasato University
• Principal Investigator: NAGAI MAKIKO 北里大学, 医学部, 講師 (80420488)
• Research Collaborator: NIHIRA Tomoko ; KAWANAMI Aya
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 筋萎縮性側索硬化症 / TDP-43 / アデノ随伴ウィルス / マウスモデル / 脊髄前角細胞

Outline of Final Research Achievements

TDP-43 was identified as the major protein component of the aggregations in the affected neurons of amyotrophic lateral sclerosis (ALS) patients.We generated the transgenic mice with loxP-dsRed-loxP-TDP-43 under the control of Thy-1.This mouse expressed dsRed in neurons of brain and spinal cord.Then we crossed this mouse with VAcht-Cre mouse, which expressed Cre in motor neurons. We expected the motor neuron deaths in the spinal cords of these double transgenic mice to use as the ALS model. These double transgenic mice did not expressed the paralysis, because the insufficiency of TDP-43 protein level.
We used adeno-associated virus (AAV) vectors to overexpress the TDP-43 in the mice motor neurons. TDP-43-WT and TDP-43-A315T mice showed muscle weakness of the left hindlimb from 2 weeks of injection. We may use these mice as ALS model.

Free Research Field

筋萎縮性側索硬化症の病態解明