A soluble form of human nectin-2 impairs exocrine secretion of pancreas and formation of zymogen granules in transgenic mice

Yukiko Tomioka, Yoshikazu Fujimoto, Kanji Nakai, Kinuyo Ozaki, Sayo Yamamoto, Haruka Suyama, Masami Morimatsu, Toshihiro Ito, Etsuro Ono

Research output: Contribution to journalArticle

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Abstract

Transgenic mouse lines expressing a soluble form of human nectin-2 (hNectin-2Ig Tg) exhibited distinctive elevation of amylase and lipase levels in the sera. In this study, we aimed to clarify the histopathology and to propose the transgenic mouse lines as new animal model for characteristic pancreatic exocrine defects. The significant increase of amylase and lipase levels in sera of the transgenic lines approximately peaked at 8 weeks old and thereafter, plateaued or gradually decreased. The histopathology in transgenic acinar cells was characterized by intracytoplasmic accumulation of abnormal proteins with decrease of normal zymogen granules. The hNectin-2Ig expression was observed in the cytoplasm of pancreatic acinar cells, which was consistent with zymogen granules. However, signals of hNectin-2Ig were very weak in the transgenic acinar cells with the abnormal cytoplasmic accumulaion. The PCNA-positive cells increased in the transgenic pancreas, which suggested the affected acinar cells were regenerated. Acinar cells of hNectin-2Ig Tg had markedly small number of zymogen granules with remarkable dilation of the endoplasmic reticulum (ER) lumen containing abundant abnormal proteins. In conclusion, hNectin-2Ig Tg is proposed as a new animal model for characteristic pancreatic exocrine defects, which are due to the ER stress induced by expression of mutated cell adhesion molecule that is a soluble form of human nectin-2.

Original languageEnglish
Pages (from-to)196-202
Number of pages7
JournalBiochemistry and Biophysics Reports
Volume5
DOIs
Publication statusPublished - Mar 1 2016

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Exocrine Pancreas
Enzyme Precursors
Acinar Cells
Secretory Vesicles
Transgenic Mice
Amylases
Lipase
Animals
Defects
Proliferating Cell Nuclear Antigen
Cell Adhesion Molecules
Animal Models
Proteins
Cells
Endoplasmic Reticulum Stress
Serum
Endoplasmic Reticulum
Dilatation
Pancreas
Cytoplasm

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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A soluble form of human nectin-2 impairs exocrine secretion of pancreas and formation of zymogen granules in transgenic mice. / Tomioka, Yukiko; Fujimoto, Yoshikazu; Nakai, Kanji; Ozaki, Kinuyo; Yamamoto, Sayo; Suyama, Haruka; Morimatsu, Masami; Ito, Toshihiro; Ono, Etsuro.

In: Biochemistry and Biophysics Reports, Vol. 5, 01.03.2016, p. 196-202.

Research output: Contribution to journalArticle

Tomioka, Yukiko ; Fujimoto, Yoshikazu ; Nakai, Kanji ; Ozaki, Kinuyo ; Yamamoto, Sayo ; Suyama, Haruka ; Morimatsu, Masami ; Ito, Toshihiro ; Ono, Etsuro. / A soluble form of human nectin-2 impairs exocrine secretion of pancreas and formation of zymogen granules in transgenic mice. In: Biochemistry and Biophysics Reports. 2016 ; Vol. 5. pp. 196-202.
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