Systemic Overexpression of TNFα-converting Enzyme Does Not Lead to Enhanced Shedding Activity In Vivo

Masaki Yoda, Tokuhiro Kimura, Takahide Tohmonda, Hideo Morioka, Morio Matsumoto, Yasunori Okada, Yoshiaki Toyama, Keisuke Horiuchi

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

TNFα-converting enzyme (TACE/ADAM17) is a membrane-bound proteolytic enzyme with a diverse set of target molecules. Most importantly, TACE is indispensable for the release and activation of pro-TNFα and the ligands for epidermal growth factor receptor in vivo. Previous studies suggested that the overproduction of TACE is causally related to the pathogenesis of inflammatory diseases and cancers. To test this hypothesis, we generated a transgenic line in which the transcription of exogenous Tace is driven by a CAG promoter. The Tace-transgenic mice were viable and exhibited no overt defects, and the quantitative RT-PCR and Western blot analyses confirmed that the transgenically introduced Tace gene was highly expressed in all of the tissues examined. The Tace-transgenic mice were further crossed with Tace-/+ mice to abrogate the endogenous TACE expression, and the Tace-transgenic mice lacking endogenous Tace gene were also viable without any apparent defects. Furthermore, there was no difference in the serum TNFα levels after lipopolysaccharide injection between the transgenic mice and control littermates. These observations indicate that TACE activity is not necessarily dependent on transcriptional regulation and that excess TACE does not necessarily result in aberrant proteolytic activity in vivo.

Original languageEnglish
Article numbere54412
JournalPloS one
Volume8
Issue number1
DOIs
Publication statusPublished - 2013 Jan 14

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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