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Kinji Ohno | OMICS International
ISSN: 2329-6895

Journal of Neurological Disorders
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Kinji Ohno

Nagoya University Graduate School of Medicine, Japan

Biography

He constructed a recombinant adeno-associated virus serotype 8 (AAV8) carrying human COLQ. We injected AAV8-COLQ to the tail vein of Colq-/- mice. In four weeks after injection, the NMJ ultrastructure was normalized, and electrophysiological features of the NMJ signal transmission were normalized but not completely. In six weeks after injection, motor functions of the treated mice normalized completely; ColQ-tailed AChE was specifically anchored to the NMJ by immunostaining; the amount of AChE was restored to 89% of the wild-type. He also injected AAV8-COLQ intramuscularly to the right anterior tibial muscle, and found that ColQ-tailed AChE was expressed to ~15% of the wild-type in non-injected forelimbs and left hindlimb. He next characterized the molecular basis of this efficient recovery. We first confirmed that ColQ-tailed AChE can be specifically targeted to NMJ by an in vitro overlay assay in Colq-/- mice muscle sections. He then injected AAV1-COLQ-IRES-EGFP into the left tibialis anterior and detected AChE in non-injected limbs. Furthermore, in vivo injection of recombinant ColQ-tailed AChE protein complex into the gluteus maximus muscle of Colq-/- mice led to accumulation of AChE in non-injected forelimbs. He demonstrated for the first time in vivo that the ColQ protein contains a tissue-targeting signal that is sufficient for anchoring itself to the NMJ. He propose that the protein-anchoring therapy is potentially applicable to a broad spectrum of diseases affecting extracellular matrix molecules.

Research Interest

Molecular pathomechanisms and the regulations of defective neuromuscular transmission defects, Neurology, Neurodegenerative disorders

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