Trypsin in pancreatitis: The culprit, a mediator, or epiphenomenon?

Table 1 Trypsinogen activation in hereditary pancreatitis-related genetic mouse models: Representative studies

Genetic mouse model	Genetic modification	Spontaneous pancreatitis	Increase in basal trypsin activity	Effects of pancreatitis inducers	Trypsinogen activation in CER-AP	Ref.
PRSS1R122H	Mutated human PRSS1R122H or WT PRSS1 gene expressed under full-length elastase promoter	No	No	Severity of AP induced with CER, LPS or ethanol increased in the order: WT mouse < PRSS1 < PRSS1R122H	Increased in the order: WT mouse < PRSS1 < PRSS1R122H	[42]
PRSS1
PRSS2	Transgenic mice similarly expressing human PRSS2 gene	Focal areas (< 10% of total pancreas)	ND	CER-AP was more severe in PRSS2 expressing mice	ND	[44]
PRSS1/PRSS2	Compound mice co-expressing WT PRSS1 and PRSS2 or PRSS1R122H and PRSS2 from their native promoters	Yes, in homozygous PRSS1R122H/PRSS2 mice, but not in PRSS1/PRSS2 mice	ND	One i.p. injection of low-dose CER induced pancreatitis in PRSS1R122H/PRSS2 but not in PRSS1/PRSS2 mice	ND	[46]
PRSS1R122H/PRSS2
PRSS1/PRSS2+ PRSS2	Compound PRSS1/PRSS2 or PRSS1R122H/PRSS2 mice were further crossed with mice expressing WT PRSS2	Yes, in PRSS1R122H/PRSS2+ PRSS2 mice, but not in PRSS1/PRSS2+ PRSS2 mice	ND	ND	ND	[46]
PRSS1R122H/PRSS2+ PRSS2
T7D23A knock-in	Heterozygous p.D23A mutation in the TAP part of T7 trypsinogen gene	Yes	Yes	ND	ND	[38]
T7K24R knock-in	Heterozygous p.K23R mutation in the TAP part of T7 trypsinogen gene	No	No	CER-AP was aggravated	Increased	[43]
Ctrb1-del	Mice deficient in CTRB1 chymotrypsin that promotes trypsinogen degradation	No	No	CER-AP was aggravated	Increased	[39,49]
T7K24R×Ctrb1-del	Compound mice carrying both the trypsinogen mutant T724KR and chymotrypsin Ctrb1 deletion alleles	Yes	ND	ND	ND	[49]

CER: Cerulein; LPS: Lipopolysaccharide; ND: Not determined; TAP: Trypsinogen activation peptide.