In vivo optical imaging of motor neuron autophagy in a mouse model of amyotrophic lateral sclerosis

Feng Feng Tian, Nobutoshi Morimoto, Wen Tao Liu, Yasuyuki Ohta, Kentaro Deguchi, Kazunori Miyazaki, Koji Abe

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Autophagy is involved in the pathological process of motor neuron death in amyotrophic lateral sclerosis (ALS). We have generated a novel double transgenic (DTg) mouse line by mating a green fluorescent protein (GFP)-fused microtubuleassociated protein 1 light chain 3 (LC3) transgenic (LC3-Tg) mouse and a G93A mutant human Cu/Zn superoxide dismutase (mSOD1) transgenic (mSOD1-Tg) mouse. In vivo imaging of autophagy with these novel DTg mice was conducted at 10 (presymptomatic), 17 (early symptomatic) and 19 (late symptomatic) weeks of age. Fluorescence imaging analysis revealed a strong fluorescent signal in vivo over the T3-S1 level at 17 and 19 weeks of age only in the DTg mice. Ex vivo autophagy imaging of spinal cord sections (20 μm) also showed a progressive increase of the fluorescence signal from 17 to 19 weeks in DTg mice in the anterior horn at the L4-5 level, and the fluorescence signals were clearly observed in the gray matter of the spinal cord with a progressive increase of the signal and decreases in large motor neurons. Protein gel blot analysis revealed maximum LC3-I and LC3-II expressions at 19 weeks, consistent with the results from the in vivo autophagy imaging experiment. This method could also be applied as a unique tool for clarifying the role of autophagy, and to monitor the pathologic processes involving autophagy not only in ALS, but also other neurological diseases.

Original languageEnglish
Pages (from-to)985-992
Number of pages8
JournalAutophagy
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 2011

Keywords

  • ALS
  • DTg mice
  • GFP-LC3
  • In vivo autophagy imaging
  • SOD1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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