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Comparative efficacy of expression of genes delivered to mouse sensory neurons with herpes virus vectors
Author(s) -
Davar G.,
Kramer M. F.,
Garber D.,
Roca A. L.,
Andersen J. K.,
Bebrin W.,
Coen D. M.,
KoszVnenchak M.,
Knipe D. M.,
Breakefield X. O.,
Isacson O.
Publication year - 1994
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.903390103
Subject(s) - trigeminal ganglion , biology , herpes simplex virus , ganglion , microbiology and biotechnology , in situ hybridization , axoplasmic transport , vector (molecular biology) , reporter gene , virology , sensory system , gene expression , gene , virus , anatomy , neuroscience , genetics , recombinant dna
To achieve gene delivery to sensory neurons of the trigeminal ganglion, thymidine kinase‐negative (TK − ) herpes simplex viruses (HSV) containing the reporter gene lacZ (the gene for E. coli β‐galactosidase) downstream of viral (in vectors RH116 and tk LTRZ1) or mammalian (in vector NSE‐lacZ‐ tk ) promoters were inoculated onto mouse cornea and snout. Trigeminal ganglia were removed 4, 14, 30, and 60 days after inoculation with vectors and histochemically processed with 5‐bromo‐4‐chloro‐3 indolyl‐beta‐galactoside (X‐Gal). With vector tk LTRZ1, large numbers of labeled neurons were observed in rostromedial and central trigeminal ganglion at 4 days after inoculation. A gradual decline in the number of labeled neurons was observed with this vector at subsequent time points. With vectors RH116 and NSE‐lacZ‐ tk , smaller numbers of labeled neurons were seen at 4 days following inoculation than were observed with vector tk LTRZ1. No labeled neurons could be observed at 14 days after inoculation with vectors RH116 and NSE‐lacZ‐ tk . Immunocytochemistry for E. coli β‐galactosidase and in situ hybridization to HSV latency‐associated transcripts revealed labeled neurons in regions of the trigeminal ganglion similar to that observed with X‐Gal staining. A comparable distribution of labeled neurons in trigeminal ganglion was also observed after application of the retrograde tracer Fluoro‐Gold to mouse cornea and snout. These data provide evidence that retrogradely transported tk − herpes virus vectors can be used to deliver a functional gene to sensory neurons in vivo in an anatomically predictable fashion. © 1994 Wiley‐Liss, Inc.