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Adenoviral-mediated Gene Transfer to Mouse Salivary Glands

Gene Therapy and Therapeutics Branch

B.J. Baum

Gene Therapy and Therapeutics Branch

S. Yamano

Gene Therapy and Therapeutics Branch

M.H. Mankani

Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bldg. 10, 1N113, MSC-1190, Bethesda, MD 20892-1190

D. Sun

Gene Therapy and Therapeutics Branch

M. Jonsson

Gene Therapy and Therapeutics Branch

C. Davis

Gene Therapy and Therapeutics Branch

F.L. Graham

Dept. of Biology, Dept of Pathology, Health Sciences Centre, McMaster University, Hamilton, Ontario, Canada

J. Gauldie

Dept of Pathology, Health Sciences Centre, McMaster University, Hamilton, Ontario, Canada

J.C. Atkinson

Gene Therapy and Therapeutics Branch, Corresponding author, jatkinson{at}dir.nidcr.nih.gov

Adenoviral vectors effectively transfer genes to rat salivary glands. However, potent immune responses limit their use in vivo. Mice offer more opportunities than rats for the study of these immune processes. We first established conditions for infection of mouse salivary glands, with an adenoviral vector. The effects of time, viral dose, viral diluent buffer volume, and dexamethasone on expression of a transgene, luciferase, were determined by means of the recombinant vector AdCMVluc. Optimal luciferase expression was observed when the vector was suspended in 50 µL of buffer. This volume completely filled the gland parenchyma and slightly distended the capsule. Dexamethasone increased immediate transgene expression and reduced the acute inflammation one day following viral administration, but did not alter subsequent mononuclear inflammation or transgene expression 14 or 28 days later. An adenoviral vector encoding either antiinflammatory cytokine IL-4 or IL-10 was co-administered with AdCMVluc to increase transgene expression at 14 and 28 days. While this strategy did not extend the duration of luciferase expression, co-administration of AdCMVIL-10 with AdCMVluc almost completely eliminated the chronic inflammatory infiltrate in the glands after 28 days. This study demonstrates that adenoviral-mediated gene transfer to mouse submandibular glands is possible by intraductal cannulation and that reduction of either the acute or chronic inflammatory infiltrates was insufficient to increase long-term transgene expression in this tissue.

Key Words: Salivary glands • gene transfer • gene therapy.

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Journal of Dental Research, Vol. 79, No. 2, 701-708 (2000)
DOI: 10.1177/00220345000790020201


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