Pathophysiology of acute experimental pancreatitis: Lessons from genetically engineered animal models and new molecular approaches

The incidence of acute pancreatitis is growing and worldwide
population-based studies report a doubling or tripling since the
1970s. 25% of acute pancreatitis are severe and associated with
histological changes of necrotizing pancreatitis. There is still no
specific medical treatment for acute pancreatitis. The average
mortality resides around 10%. In order to develop new specific
medical treatment strategies for acute pancreatitis, a better
understanding of the pathophysiology during the onset of acute
pancreatitis is necessary. Since it is difficult to study the early
acinar events in human pancreatitis, several animal models of acute
pancreatitis have been developed. By this, it is hoped that clues
into human pathophysiology become possible. In the last decade,
while employing molecular biology techniques, a major progress has
been made. The genome of the mouse was recently sequenced. Various
strategies are possible to prove a causal effect of a single gene
or protein, using either gain-of-function (i.e., overexpression of
the protein of interest) or loss-of-function studies (i.e., genetic
deletion of the gene of interest). The availability of transgenic
mouse models and gene deletion studies has clearly increased our
knowledge about the pathophysiology of acute pancreatitis and
enables us to study and confirm in vitro findings in animal models.
In addition, transgenic models with specific genetic deletion or
overexpression of genes help in understanding the role of one
specific protein in a cascade of inflammatory processes such as
pancreatitis where different proteins interact and co-react. This
review summarizes the recent progress in this field. Copyright (c)
2005 S. Karger AG, Basel.