ArticleThe Journal of clinical investigation2020
Trypsin activity governs increased susceptibility to pancreatitis in mice expressing human PRSS1R122H.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 3 of them syntheses that pooled it.
What it found
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Who cites it
36 citing papers in PubMed, 3 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Trypsinogen (PRSS1 and PRSS2) gene dosage correlates with pancreatitis risk across genetic and transgenic studies: a systematic review and re-analysis.Human genetics · 2022Pooled it
- Scale and Scope of Gene-Alcohol Interactions in Chronic Pancreatitis: A Systematic Review.Genes · 2021Pooled it
- Experimental Acute Pancreatitis Models: History, Current Status, and Role in Translational Research.Frontiers in physiology · 2020Pooled it
- Pathologically relevant trypsinogen activation in pancreatitis.American journal of physiology. Gastrointestinal and liver physiology · 2026Review
- Advancing Gene Therapy for Pancreatitis: From Genetic Insights to Clinical Translation.Research (Washington, D.C.) · 2026Review
- From single-pathway cascade to network pathophysiology: how genetically engineered mouse models reshaped our understanding of pancreatitis.Frontiers in physiology · 2026Review
- Discovery of an autoinhibited conformation in mesotrypsin reveals a strategy for selective serine protease inhibition.Science advances · 2025Article
- Overexpression of Tn antigen induces chronic pancreatitis in mice.Scientific reports · 2025Article
- Genetics and clinical implications of SPINK1 in the pancreatitis continuum and pancreatic cancer.Human genomics · 2025Review
- Trypsin in pancreatitis: The culprit, a mediator, or epiphenomenon?World journal of gastroenterology · 2024Review
- Secretagogue-induced pancreatitis in mice devoid of chymotrypsin.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Albumin promoter-driven FlpO expression induces efficient genetic recombination in mouse liver.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Article
- Upregulation of the ERRγ-VDAC1 axis underlies the molecular pathogenesis of pancreatitis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Genetically Engineered Mouse Models Shine New Light on Decades-old Story of Trypsin in Pancreatitis.Gastroenterology · 2023Article
- Mouse model of PRSS1 p.R122H-related hereditary pancreatitis highlights context-dependent effect of autolysis-site mutation.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2023Article
- Article
- Preclinical testing of dabigatran in trypsin-dependent pancreatitis.JCI insight · 2022Article
- Rate of Autoactivation Determines Pancreatitis Phenotype in Trypsinogen Mutant Mice.Gastroenterology · 2022Article
- Expanding ACMG variant classification guidelines into a general framework.Human genomics · 2022Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 1 country.
Funding
Abstract
Currently, an effective targeted therapy for pancreatitis is lacking. Hereditary pancreatitis (HP) is a heritable, autosomal-dominant disorder with recurrent acute pancreatitis (AP) progressing to chronic pancreatitis (CP) and a markedly increased risk of pancreatic cancer. In 1996, mutations in PRSS1 were linked to the development of HP. Here, we developed a mouse model by inserting a full-length human PRSS1R122H gene, the most commonly mutated gene in human HP, into mice. Expression of PRSS1R122H protein in the pancreas markedly increased stress signaling pathways and exacerbated AP. After the attack of AP, all PRSS1R122H mice had disease progression to CP, with similar histologic features as those observed in human HP. By comparing PRSS1R122H mice with PRSS1WT mice, as well as enzymatically inactivated Dead-PRSS1R122H mice, we unraveled that increased trypsin activity is the mechanism for R122H mutation to sensitize mice to the development of pancreatitis. We further discovered that trypsin inhibition, in combination with anticoagulation therapy, synergistically prevented progression to CP in PRSS1R122H mice. These animal models help us better understand the complex nature of this disease and provide powerful tools for developing and testing novel therapeutics for human pancreatitis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.