PRSS1, encoding the cationic trypsinogen, is a crucial gene. Trypsinogen is an enzyme precursor that, when activated to trypsin, plays a key role in the digestive process by initiating the breakdown of proteins in the small intestine. Its abnormal activation or function can lead to pancreatitis, highlighting its importance in pancreatic health [1,2,3,4,5,6].

Mutations in PRSS1 cause human hereditary pancreatitis. Transgenic mice expressing mutant forms of human PRSS1, like PRSS1R122H, develop more severe pancreatitis upon induction by caerulein, lipopolysaccharide, ethanol, or a high-fat diet. Their pancreata show more DNA damage, apoptosis, collagen deposition, increased trypsin activity, and inflammatory cell infiltration, suggesting that mutant PRSS1 promotes inflammation and exacerbates pancreatitis [3].

In conclusion, PRSS1 is essential for normal pancreatic digestive function. Studies using transgenic mouse models expressing mutant PRSS1 have revealed its significant role in the development and severity of pancreatitis. Understanding PRSS1's function and its mutant-associated phenotypes in vivo helps in deciphering the pathogenesis of pancreatitis and may potentially lead to new therapeutic strategies for this disease [3].

References:

1. Girodon, Emmanuelle, Rebours, Vinciane, Chen, Jian Min, Ferec, Claude, Bienvenu, Thierry. 2020. Clinical interpretation of PRSS1 variants in patients with pancreatitis. In Clinics and research in hepatology and gastroenterology, 45, 101497. doi:10.1016/j.clinre.2020.07.004. https://pubmed.ncbi.nlm.nih.gov/33257277/

2. Zou, Wen-Bin, Tang, Xin-Ying, Zhou, Dai-Zhan, Chen, Jian-Min, Liao, Zhuan. 2018. SPINK1, PRSS1, CTRC, and CFTR Genotypes Influence Disease Onset and Clinical Outcomes in Chronic Pancreatitis. In Clinical and translational gastroenterology, 9, 204. doi:10.1038/s41424-018-0069-5. https://pubmed.ncbi.nlm.nih.gov/30420730/

3. Huang, Haojie, Swidnicka-Siergiejko, Agnieszka Katarzyna, Daniluk, Jaroslaw, Ji, Baoan, Logsdon, Craig D. 2019. Transgenic Expression of PRSS1R122H Sensitizes Mice to Pancreatitis. In Gastroenterology, 158, 1072-1082.e7. doi:10.1053/j.gastro.2019.08.016. https://pubmed.ncbi.nlm.nih.gov/31419436/

4. Masson, Emmanuelle, Chen, Jian-Min, Audrézet, Marie-Pierre, Cooper, David N, Férec, Claude. 2013. A conservative assessment of the major genetic causes of idiopathic chronic pancreatitis: data from a comprehensive analysis of PRSS1, SPINK1, CTRC and CFTR genes in 253 young French patients. In PloS one, 8, e73522. doi:10.1371/journal.pone.0073522. https://pubmed.ncbi.nlm.nih.gov/23951356/

5. Singh, Vikesh K, Yadav, Dhiraj, Garg, Pramod K. . Diagnosis and Management of Chronic Pancreatitis: A Review. In JAMA, 322, 2422-2434. doi:10.1001/jama.2019.19411. https://pubmed.ncbi.nlm.nih.gov/31860051/

6. Németh, Balázs Csaba, Sahin-Tóth, Miklós. 2014. Human cationic trypsinogen (PRSS1) variants and chronic pancreatitis. In American journal of physiology. Gastrointestinal and liver physiology, 306, G466-73. doi:10.1152/ajpgi.00419.2013. https://pubmed.ncbi.nlm.nih.gov/24458023/