A neural cell-type-specific expression system using recombinant adenovirus vectors.
We demonstrated neural cell-type-specific gene expression using an adenovirus vector, which is useful for delivering foreign genes into quiescent neural cells. We produced eight recombinant replication-defective adenoviruses carrying the lacZ reporter gene driven by various promoters, including those of the L7/PCP2 gene (highly restricted expression in cerebellar Purkinje cells), and the myelin basic protein (in oligodendrocytes) gene. We demonstrated in vitro and in vivo promoter-driven, neural cell-type-specific gene expression by recombinant adenoviruses. The genes were transferred into these recombinant adenoviruses and expressed with high levels of efficiency in vitro and in vivo. In primary culture, the recombinant adenoviruses AdexL7-NL-LacZ and AdexMBP-NL-LacZ appeared to be expressed in a Purkinje cell and oligodendrocyte-specific manner. Introduction of 10(8) pfu of these viruses into the adult rat cerebellum by stereotactic injection yielded neural cell-type-specific expression without apparent toxicity to the animals. Thus, adenovirus vectors are useful for cell-type-specific therapeutic uses and in studies requiring neural cell-type-specific gene expression.
Hashimoto
M
M
Molecular Neurobiology Laboratory, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Aruga
J
J
Hosoya
Y
Y
Kanegae
Y
Y
Saito
I
I
Mikoshiba
K
K
D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors; D006801:Humans; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D004676:Myelin Basic Protein / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009836:Oligodendroglia / Q000502:physiology; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis
D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; C091104:Purkinje cell protein L7; D011993:Recombinant Fusion Proteins