While chronic pancreatitis (CP) is a relatively common disease, it remains difficult to treat. Chronic pancreatitis (CP) this is defined as a continuous or recurrent inflammatory pancreatic disease characterized by progressive and irreversible changes in pancreatic morphology. According to previous studies, mutations in genes encoding digestive proteases or their inhibitors often promote the development of acute pancreatitis and gradually turns into chronic pancreatitis (CP).
Although trypsin activation or persistence has an important role in initiating the pancreatitis cascade, other factors like misfolding enzymes and endoplasmic reticulum (ER) stress may be contributing factors to recurrent inflammatory events which result in chronic pancreatitis (CP). In addition, hereditary CP can also be mediated by mechanisms unrelated to trypsin activity. There is an urgent need to develop reliable, validated animal models which can define the pathological mechanisms of CP and facilitate the evaluation of new therapy in preclinical trials. Now, we introduce three of the most recently reported animal models of chronic pancreatitis to provide some references for your research.
The Heterozygous SPINK1 c.194+2T>C mutation can directly lead to chronic pancreatitis (CP) without any cofactors, Spink1+/+ mice bred from Spink1+/− mice and C57BL/6 mice have normal pancreatic histological features which shows that heterozygous Spink1 mutations patients can have healthy offspring, it also provides a basis for prenatal screening for patients.
Sun C, Liu M, An W, et al. Heterozygous Spink1 c. 194+ 2T> C mutant mice spontaneously develop chronic pancreatitis[J]. Gut, 2020, 69(5): 967-968.
The T7D23A mouse model contains a heterozygous c.68A>C (p.D23A) mutation in mouse cationic trypsinogen, yielding a T7 isoform. This novel model presents the clinical characteristics of human pancreatitis which primarily develops into acute pancreatitis before proceeding into irreversible chronic pancreatitis (CP).
Geisz A, Sahin-Tóth M. A preclinical model of chronic pancreatitis driven by trypsinogen autoactivation[J]. Nature communications, 2018, 9(1): 1-9.
CPA1 N256K mutation mice contain a human CPA1 mutation (p.N256K) in the mouse Cpa1 locus, which leads to enzyme misfolding and stimulate chronic pancreatitis (CP). This is the first mouse model that recapitulates features of digestive enzyme misfolding and associated endoplasmic reticulum (ER) stress, which makes it an ideal model to test the effects of various environmental insults (alcohol, smoking, high-fat diet) or pharmaceuticals on the progression of chronic pancreatitis.
Hegyi E, Sahin-Tóth M. Human CPA1 mutation causes digestive enzyme misfolding and chronic pancreatitis in mice[J]. Gut, 2019, 68(2): 301-312.