Transgenic mice overexpressing PG1 display corneal opacity and severe inflammation in the eye

Min Kyeung Choi, Minh Thong Le, Hye Sun Cho, Juyoung Lee, Hyoim Jeon, Se Yeoun Cha, Manheum Na, Taehoon Chun, Jin Hoi Kim, Hyuk Song, Chankyu Park

Research output: Contribution to journalArticlepeer-review

Abstract

Antimicrobial peptides (AMPs) are of interest as alternatives to antibiotics or immuno-modulators. We generated and characterized the phenotypes of transgenic mice overexpressing protegrin 1 (PG1), a potent porcine cathelicidin. No obvious differences were observed between PG1 transgenic and wild-type mice in terms of growth, development, general behaviour, and the major immune cell population. However, PG1 transgenic mice intranasally infected with Staphylococcus aureus resulted in a reduction in microscopic pulmonary injury, improved clearance of bacteria, and lower proinflammatory cytokine secretion, compared to those of wild-type mice. On the other hand, approximately 25% of PG1 transgenic mice (n = 54/215) showed corneal opacity and developed inflammation in the eye, resulting ultimately in phthisis bulbi. Immunohistochemical analyses revealed that PG1 and its activator, neutrophil elastase, localized to the basal cells of the cornea and glands in eyelids, respectively. In addition, apoptosis indicated by a Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive signal was detected from flat cells of the cornea. Our study suggests that the expression regulation or localization of AMPs such as PG1 is important to prevent their adverse effects. However, our results also showed that the cytotoxic effects of PG1 on cells could be tolerated in animals, except for the eyes.

Original languageEnglish
Article number1586
Pages (from-to)1-19
Number of pages19
JournalInternational journal of molecular sciences
Volume22
Issue number4
DOIs
Publication statusPublished - 2021 Feb

Keywords

  • Antimicrobial peptide
  • Cathelicidin
  • Corneal opacity
  • Protegrin
  • Transgenic mice

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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