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How mice help us to understand acute pancreatitis

Acute pancreatitis is a common condition with a self-limiting course in most cases and a severe form associated with a significant risk of morbidity and mortality. There is still no specific medical treatment for this disorder, and 25% of acute pancreatitis cases are severe and associated with histological changes of necrotizing pancreatitis. The average mortality resides around 10%.The incidence of acute pancreatitis is growing and worldwide population-based studies report a doubling or tripling since the 1970s.

In order to develop urgently needed specific medical treatment strategies for acute pancreatitis, a better understanding of the pathophysiology during the onset of acute pancreatitis is necessary. The anatomic position and relationships of the pancreas make direct observation of pancreatic pathology and biopsies difficult or almost impossible. Therefore, most of our pathophysiological concepts are based on animal studies. Several animal models of acute pancreatitis have been developed. By this, it is hoped that clues into human pathophysiology become possible.

Major progress has been made with the employment of molecular biology techniques. With the sequencing of the mouse genome, 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.

Two papers published in the journal Digestion give an overview of the current state of research, as well as the problems and questions still to be investigated.

Carla Holmes | alfa
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