From the Departments of Internal Medicine and Pharmacology,
Cardiovascular Center and Center on Aging, University of Iowa College of
Medicine, and Veterans Administration Medical Center, Iowa City.
Correspondence to Donald D. Heistad, MD, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242. E-mail donald-heistad{at}uiowa.edu
Background and Purpose—Gene transfer
to cerebral blood vessels has been accomplished in rats and dogs by
injection of replication-deficient adenovirus into cerebrospinal fluid.
In this study we examined transgene expression after injection of
adenovirus into the cerebrospinal fluid of mice. Responses were
observed in ICR mice and C57BL/6 mice, which are outbred and inbred
strains, respectively.
Methods—We injected replication-deficient recombinant adenovirus
expressing nuclear targeted ß-galactosidase, driven by either the
Rous sarcoma virus promoter (AdRSV-ßGal) or the cytomegalovirus
promoter (AdCMV-ßGal), into the cisterna magna of
anesthetized ICR and C57BL/6 strains of mice. The brains were
examined from 1 to 21 days after injection by chemiluminescent enzyme
activity assay or histochemical staining.
Results—After injection of AdRSV-ßGal, expression of
ß-galactosidase in ICR mice peaked on day 7 and returned to basal by
day 14. Expression of ß-galactosidase in C57BL/6 mice was maximal on
days 7 to 14 and was minimal by day 21 after injection of AdRSV-ßGal.
After injection of AdCMV-ßGal in C57BL/6 mice, peak expression of
transgene occurred on day 1 and was greatly diminished by day 3.
Transgene expression was observed primarily on the ventral surface of
the brain, with preferential expression in
leptomeninges and adventitia along the major cerebral
arteries of that region.
Conclusions—Injection of recombinant adenovirus in the cisterna
magna resulted in transgene expression in leptomeninges
and perivascular tissue of cerebral blood vessels in two strains of
mice. The CMV promoter elicited rapid but short-lived expression of the
transgene, while the RSV promoter elicited slower, more sustained
transgene expression. Expression of AdRSV transgene was prolonged in
C57BL/6 mice compared with ICR mice. This approach for gene transfer
may be useful to study cerebral vascular biology in genetically altered
strains of mice.
CNS
Growth Factor Research Laboratory,
Massachusetts General Hospital,
Boston, Massachusetts
© 1998 American Heart Association, Inc.
Original Contributions
Adenovirus-Mediated Gene Transfer In Vivo to Cerebral Blood Vessels and Perivascular Tissue in Mice
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