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Adenovirus-mediated gene transfer in olfactory neuronsin vivo

✍ Scribed by Zhao, Haiqing ;Otaki, Joji M. ;Firestein, Stuart

Publisher
John Wiley and Sons
Year
1996
Tongue
English
Weight
949 KB
Volume
30
Category
Article
ISSN
0022-3034

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✦ Synopsis

We used recombinant adenoviruses as a means of expressing exogenous genes in olfactory neurons in vivo. A replication incompetent adenovirus (type 5, Ad5) carrying the reporter gene lacZ, which codes for the enzyme 8-galactosidase (,&Gal), was applied in solution to the olfactory epithelia of rats. The expression of lacZ was controlled by the cytomegalovirus immediate-early promoter /enhancer. @-Gal expression was observed 1 day postinfection and was maximal at 3-10 days, although it could be detected for at least 21 days postinfection. Expression patterns were heterogeneous, ranging from a few percent to over 25% of the cells in different regions of both turbinate and septa1 epithelium. Staining was stronger in the olfactory versus respiratory epithelia. In olfactory epithelium staining was almost entirely restricted to olfactory neurons. @-Gal staining was also ob-served in the olfactory axons so that nerve bundles could be traced to their targets in the glomerular layer of the olfactory bulb. Intense staining of some glomeruli was evident as long a s 21 days postinfection. There was no evidence of cell loss or tissue damage due to viral infection. These results demonstrate that it is possible to use recombinant Ad5 for expressing foreign genes in olfactory neurons. This technique could be used in olfactory neurons to increase expression levels of olfactory specific genes, including the odor receptor, putative guidance and growth molecules, or elements of the transduction cascade, in order to elucidate their biological functions in

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