Spink1-flox Mouse

Spink1, or Serine Peptidase Inhibitor Kazal Type 1, is a secreted protein best known as a protease inhibitor of trypsin in the pancreas. Structurally similar to epidermal growth factor (EGF), it can modulate tumor malignancies by activating the downstream signaling of epidermal growth factor receptor (EGFR) in cancer cells [1].

In mice, heterozygous Spink1 deficiency promotes trypsin-dependent chronic pancreatitis. Prolonged cerulein stimulation in heterozygous Spink1-deleted mice (Spink1-KOhet) led to increased intrapancreatic trypsin activity, more severe acute pancreatitis, and progression to chronic pancreatitis. Also, trypsinogen mutant mice carrying the Spink1-KOhet allele had more severe chronic pancreatitis [2]. Moreover, heterozygous Spink1 c.194 + 2T>C mutation in mice promotes the development of chronic pancreatitis after an acute attack through elevated IL-33 level and induction of M2 polarization in coordination with pancreatic stellate cell activation [3].

In conclusion, Spink1 plays a crucial role in pancreatic function, especially in relation to trypsin regulation. Mouse models with Spink1 deficiency have revealed its significance in the development of chronic pancreatitis, providing insights into the disease mechanism and potentially guiding the development of new therapeutic strategies for pancreatitis-related diseases.