RRC ID 27883
著者 Tian F, Morimoto N, Liu W, Ohta Y, Deguchi K, Miyazaki K, Abe K.
タイトル In vivo optical imaging of motor neuron autophagy in a mouse model of amyotrophic lateral sclerosis.
ジャーナル Autophagy
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 microtubule-associated 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.
巻・号 7(9)
ページ 985-92
公開日 2011-9-1
DOI 10.4161/auto.7.9.16012
PII 16012
PMID 21628996
MeSH Amyotrophic Lateral Sclerosis / diagnosis* Amyotrophic Lateral Sclerosis / pathology* Animals Astrocytes / metabolism Astrocytes / pathology Autophagy* Cell Count Diagnostic Imaging / methods* Disease Models, Animal Fluorescent Antibody Technique Green Fluorescent Proteins / metabolism Humans Mice Mice, Transgenic Microtubule-Associated Proteins / metabolism Motor Neurons / pathology* Optical Phenomena* Phagosomes / metabolism Recombinant Fusion Proteins / metabolism
IF 9.77
引用数 37
WOS 分野 CELL BIOLOGY
リソース情報
実験動物マウス RBRC00806