1. Targeting functional subtypes of spinal motoneurons and skeletal muscle fibers in vivo by intramuscular injection of adenoviral and adeno-associated viral vectors.
- Author
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Martinov VN, Sefland I, Walaas SI, Lømo T, Njå A, and Hoover F
- Subjects
- Animals, Axonal Transport, Female, Ganglia, Spinal cytology, Ganglia, Spinal metabolism, Green Fluorescent Proteins, Luminescent Proteins genetics, Luminescent Proteins metabolism, Male, Mice, Mice, Inbred Strains, Motor Neurons cytology, Motor Neurons virology, Muscle Fibers, Fast-Twitch cytology, Muscle Fibers, Fast-Twitch metabolism, Muscle Fibers, Skeletal cytology, Muscle Fibers, Skeletal virology, Muscle Fibers, Slow-Twitch cytology, Muscle Fibers, Slow-Twitch metabolism, Muscle, Skeletal cytology, Muscle, Skeletal virology, Rats, Rats, Wistar, Spinal Nerves cytology, Spinal Nerves metabolism, Transduction, Genetic methods, Adenoviruses, Human genetics, Dependovirus genetics, Gene Targeting, Genetic Vectors, Motor Neurons metabolism, Muscle Fibers, Skeletal metabolism, Muscle, Skeletal metabolism
- Abstract
We report that functional subtypes of spinal motoneurons and skeletal muscle fibers can be selectively transduced using replication-defective adenoviral (ADV) or adeno-associated (AAV) viral vectors. After intramuscular injection in adult rodents, ADV vectors transduced both fast-twitch and slow-twitch skeletal muscle fibers. Intramuscular injection of ADV vectors also caused transduction of spinal motoneurons and dorsal root ganglion cells. However, only neurons innervating the injected muscle were transduced, as shown by co-injection of a retrograde axonal tracer. In adult male rats it is therefore possible to transduce fast or slow spinal motoneurons and muscle fibers selectively since in these animals, the extensor digitorum longus and soleus muscles contain almost exclusively fast or slow motor units, respectively. In rats, AAV vectors transduced muscle fibers in the predominantly fast extensor digitorum longus but not in the predominantly slow soleus muscle. We did not observe any transduction of spinal motoneurons following intramuscular injection of AAV vectors. These results show that physiologically and clinically important subpopulations of cells in the neuromuscular system can be selectively transduced by viral vectors.
- Published
- 2002
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