Transduction of murine cerebellar neurons with recombinant FIV and AAV5 vectors.
Our data demonstrate that vectors derived from recombinant feline immunodeficiency virus (rFIV) and adeno-associated virus type 5 (rAAV5) transduce cerebellar cells following direct injection into the cerebellar lobules of mice. Both recombinant viruses mediated gene transfer predominantly to neurons, with up to 2500 and 1500 Purkinje cells transduced for rAAV5 or rFIV-based vectors, respectively. The vectors also transduced stellate, basket and Golgi neurons, with occasional transduction of granule cells and deep cerebellar nuclei. rAAV5 also spread outside the cerebellum to the inferior colliculus and ventricular epithelium, while rFIV demonstrated the ability to undergo retrograde transport to the physically close lateral vestibular nuclei. Thus, AAV5 and FIV-based vectors show promise for targeting neurons affected in the hereditary spinocerebellar ataxias. These vectors could be important tools for unraveling the pathophysiology of these disorders, or in testing factors which may promote neuronal survival.
Alisky
J M
JM
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Hughes
S M
SM
Sauter
S L
SL
Jolly
D
D
Dubensky
T W
TW
Staber
P D
PD
Chiorini
J A
JA
Davidson
B L
BL
D000818:Animals; D001693:Biological Transport, Active; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D000229:Dependovirus / Q000235:genetics*; D005822:Genetic Vectors; D016089:Immunodeficiency Virus, Feline / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D011689:Purkinje Cells / Q000201:enzymology; D014161:Transduction, Genetic; D019076:Transgenes; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D001616:beta-Galactosidase