Targeting functional subtypes of spinal motoneurons and skeletal muscle fibers in vivo by intramuscular injection of adenoviral and adeno-associated viral vectors.
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.
Martinov
Vladimir N
VN
Department of Physiology, University of Oslo, Oslo, Norway.
Sefland
Iren
I
Walaas
S Ivar
SI
Lømo
Terje
T
Njå
Arild
A
Hoover
Frank
F
D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D001370:Axonal Transport; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D018390:Gene Targeting; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D018656:Muscle Fibers, Fast-Twitch / Q000166:cytology / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D018657:Muscle Fibers, Slow-Twitch / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D051381:Rats; D017208:Rats, Wistar; D013127:Spinal Nerves / Q000166:cytology / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods
D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins