Chronic pancreatitis in mice by treatment with choline-deficient ethionine-supplemented diet

Exp Anim. 2010;59(4):421-9. doi: 10.1538/expanim.59.421.


Although chronic pancreatitis is a risk factor for pancreatic ductal adenocarcinoma (PDA), the relationship between chronic pancreatitis and PDA remains obscure. A critical obstacle to understanding the role of chronic pancreatitis is the lack of animal models. To develop one such model, mice were fed long-term with a choline deficient ethionine-supplemented (CDE) diet. Histological evaluation revealed that chronic pancreatitis, characterized by acinar atrophy, fibrosis and well-developed tubular complexes (TCs), was observed after 24 weeks of CDE diet treatment. Furthermore, expression of epidermal growth factor receptor (EGFR) and its ligands; serine protease inhibitor Kazal type 3 (Spink3) and transforming growth factor alpha (TGF alpha) and activation of K-Ras (GTP-Ras formation), which are frequently observed in human PDA, were indeed observed in parallel with TCs formation. Neoplastic lesions were not found after 54 weeks of treatment, suggesting that a continuation of CDE diet or another insult is required for the development of PDA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amylases / blood
  • Animal Feed / adverse effects*
  • Animals
  • Biomarkers / metabolism
  • Blotting, Western
  • Choline Deficiency / complications*
  • Choline Deficiency / pathology
  • Disease Models, Animal
  • ErbB Receptors / metabolism
  • Ethionine / administration & dosage
  • Ethionine / adverse effects*
  • Female
  • Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatitis, Chronic / etiology*
  • Pancreatitis, Chronic / pathology
  • Prostatic Secretory Proteins / metabolism
  • Transforming Growth Factor alpha / metabolism
  • Trypsin Inhibitor, Kazal Pancreatic
  • ras Proteins / metabolism


  • Biomarkers
  • Glycoproteins
  • Prostatic Secretory Proteins
  • Spink1 protein, mouse
  • Transforming Growth Factor alpha
  • Trypsin Inhibitor, Kazal Pancreatic
  • EGFR protein, mouse
  • ErbB Receptors
  • Amylases
  • ras Proteins
  • Ethionine