Genetically inducedvs.classical animal models of chronic pancreatitis: a critical comparison

Abstract

Chronic pancreatitis (CP) is an utmost complex disease that is pathogenetically linked to pancreas-intrinsic ( e.g., duct obstruction), environmental-toxic ( e.g., alcohol, smoking), and genetic factors. Studying such a complex disease naturally requires validated experimental models. In the past 2 decades, the various animal models of CP usually addressed either the pancreas-intrinsic ( e.g., the caerulein model), the environmental-toxic ( e.g., diet-induced models), or the genetic component of CP. As such, these models were far from mirroring CP in its full spectrum, and the correct choice of models was vital for valid scientific conclusions on CP. The quest for mechanistic, genetic models gave rise to models based on gene modification and transgene insertion, such as the PRSS1 and the IL-1β/IL-1β models. Recently, we witnessed the development of highly exciting models that rely on the importance of autophagy in CP, that is, the murine pancreas-specific Atg5 and LAMP2 knockout models. Today, critical comparison of these several models is more important than ever for guiding research on CP in an efficient direction. The present review outlines the characteristics of the new genetic models in comparison with the well-known classic models for CP, notes the caveats in the choice of models, and also indicates novel directions for model development.-Klauss, S., Schorn, S., Teller, S., Steenfadt, H., Friess, H., Ceyhan, G. O., Demir, I. K. Genetically induced vs. classical animal models of chronic pancreatitis: a critical comparison.

Sex as a Biological Variable: A 5-Year Progress Report and Call to Action

“…Using SABV as a guiding principle throughout the research continuum can help address key issues affecting the biomedical research enterprise, including (1) the need to identify animal models that better reflect human diseases 46,53,54 ; (2) concerns about the increased risk of adverse events or reduced treatment effectiveness in women 55,56 ; and…”

Modeling pancreatic cancer in mice for experimental therapeutics

“…Although direct role of pancreatitis, both acute and chronic, is obscure as a single factor, there is ample evidence suggesting that inflammation and pancreatitis could potentially trigger PDAC pathogenesis [78][79][80]. Both classical and genetically induced models have been used to study inflammation and pancreatitis [81][82][83]. Cerulein-based experimental models of inflammation and pancreatitis have been extensively employed for mechanistic understanding as well as for therapeutic evaluation.…”

“…One of the earliest models to study acute pancreatitis was reported in1977 by Lampel and Kern, which involved secretagogue hyperstimulation using cholecystokinin (CCK) in rat [84]. Since then, several studies have used cerulein, an orthologue of CCK, for induction of both acute and chronic pancreatitis (CP) in mice [75,81]. We have summarized key mouse models that have been used to study pancreatitis in the context of pathophysiology, potentiating PDAC, biomarker discovery, or evaluating the therapeutic modalities (Figure 2C).…”

The rise of genetically engineered mouse models of pancreatitis: A review of literature

“…While non-GEMM models of pancreatitis have proven to be, and will continue to be valuable models for investigating the underlining mechanisms of pancreatitis, the sections below will provide an overview of currently available GEMM pancreatitis models. For a more comprehensive review covering both non-GEMM models and the more popular GEMM models of pancreatitis, readers are referred to the 2018 review by Klauss et al [16]. For the remainder of this review we have limited ourselves to the models that spontaneously develop pancreatitis symptoms and do not develop pancreatic adenocarcinoma at a young age.…”