Efficient and controlled gene expression in mouse pancreatic islets by arterial delivery of tetracycline-inducible adenoviral vectors

Rui Takahashi, Hisamitsu Ishihara, Kazuma Takahashi, Akira Tamura, Suguru Yamaguchi, Takahiro Yamada, Hideki Katagiri, Yoshitomo Oka

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Gene transfer with adenovirus vectors has been used extensively for pancreatic islet research. However, infection efficiency varies among reports. We reevaluated the infection efficiency, defined here as the percentage of islet cells expressing transgenes, in mouse islets. When the isolated islets were infected with adenoviruses, the infection efficiency was found to be 30-40% and the transduced cells were distributed in the islet periphery. Collagenase treatment of isolated islets before infection increased the infection efficiency to 70%, but with suppression of glucose-stimulated insulin secretion. To explore more efficient strategies, we employed arterial delivery of virus particles to islets in situ. Delivery of adenovirus (∼ 108 particles per pancreas) through the celiac and superior mesenteric arteries is highly efficient, resulting in more than 90% transduction without impairing glucose-stimulated insulin secretion. Arterial delivery of an adenovirus harboring glycerol kinase cDNA allowed us to observe glycerol-stimulated insulin secretion from mouse islets, which was not observed when we employed the conventional method. Furthermore, the arterial delivery method combined with a tetracycline-inducible adenovirus system induced efficient and controlled transgene expression. Our data provide new insights into gene transduction methods using recombinant adenoviruses in mouse islets, and are therefore anticipated to contribute to future basic and clinical islet research applications.

Original languageEnglish
Pages (from-to)127-136
Number of pages10
JournalJournal of Molecular Endocrinology
Volume38
Issue number1-2
DOIs
Publication statusPublished - 2007 Feb

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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