Targeting Trypsin-Inflammation Axis for Pancreatitis Therapy in a Humanized Pancreatitis Model

Abstract

Acute pancreatitis especially due to alcohol and smoking goes onto chronic pancreatitis which, in turn, is a risk factor for pancreatic cancer. Because only a relatively small portion of patients with alcohol abuse and smoking develop pancreatitis, it is very likely that there are genetic underlying predisposing factors that have not been discovered that explain why certain individuals develop pancreatitis. A genetic defect in the trypsinogen gene (PRSS1 gene) causing hereditary pancreatitis is now well established. We developed a transgenic mouse using a Bacterial Artificial Chromosome harboring the full-length human PRSS1 with the key mutation of hereditary pancreatitis (PRSS1R122H). During the funding year we used this novel mouse model to determine whether PRSS1R122H predispose to pancreatitis. Our data so far indicates that mice expressing PRSS1R122H develop a more severe form of pancreatitis than wild type mice controls. We are working now in understanding the mechanisms underlying the observed effects.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2016
Accession Number
AD1033262

Entities

People

  • Aurelia Lugea
  • Stephen J Pandol

Organizations

  • Cedars-Sinai Medical Center

Tags

DTIC Thesaurus Topics

  • Acinar Cells
  • Cell Physiological Processes
  • Cells
  • Chromosomes
  • Endoplasmic Reticulum
  • Genes
  • Genetic Phenomena
  • Genetic Structures
  • Genetics
  • Inflammation
  • Medical Personnel
  • Pancreas
  • Pancreatitis
  • Risk Factors
  • Standards
  • Targeting
  • Trypsinogen

Fields of Study

  • Medicine

Readers

  • Gulf War Illness and Chronic Multisymptom Illness in Veterans.
  • Immunology
  • Molecular and Cellular Biology

Technology Areas

  • Biotechnology