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In vitro and in vivo gene therapy with CMV vector-mediated presumed dog β-nerve growth factor in pyridoxine-induced neuropathy dogs
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- Authors
- Issue Date
- 2008
- Citation
- J Vet Sci 2008, 9, 367-373
- Keywords
- dog ; gene therapy ; in vitro ; in vivo ; nerve growth factor ; neuropathy
- Abstract
- Due to the therapeutic potential of gene therapy for
neuronal injury, many studies of neurotrophic factors,
vectors, and animal models have been performed. The
presumed dog β-nerve growth factor (pdβ-NGF) was
generated and cloned and its expression was confirmed in
CHO cells. The recombinant pdβ-NGF protein reacted with
a human β-NGF antibody and showed bioactivity in PC12
cells. The pdβ-NGF was shown to have similar bioactivity to
the dog β-NGF. The recombinant pdβ-NGF plasmid was
administrated into the intrathecal space in the gene therapy
group. Twenty-four hours after the vector inoculation, the
gene therapy group and the positive control group were
intoxicated with excess pyridoxine for seven days. Each
morning throughout the test period, the dogs body weight
was taken and postural reaction assessments were made.
Electrophysiological recordings were performed twice, once
before the experiment and once after the test period. After
the experimental period, histological analysis was performed.
Dogs in the gene therapy group had no weight change and
were normal in postural reaction assessments. Electrophysiological
recordings were also normal for the gene therapy
group. Histological analysis showed that neither the axons
nor the myelin of the dorsal funiculus of L4 were severely
damaged in the gene therapy group. In addition, the dorsal
root ganglia of L4 and the peripheral nerves (sciatic nerve)
did not experience severe degenerative changes in the gene
therapy group. This study is the first to show the protective
effect of NGF gene therapy in a dog model.
- ISSN
- 1229-845X
- Language
- English
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