Pathophysiology of SPINK mutations in pancreatic development and disease.
The endogenous pancreatic trypsin inhibitor, SPINK, is believed to limit enzyme activity in the pancreas and reduce the risk of pancreatitis. Recently, mutations in the SPINK1 gene have been associated with development of both acute and chronic pancreatitis. In most patients with SPINK1 mutations, the genetic variants do not cause the disease independently, but may act in concert with other genetic or environmental factors. Recent studies, using mice in which the trypsin inhibitor gene has been deleted or overexpressed, provide novel insights into the role of SPINK in pancreatic development and pancreatitis.
Liddle
Rodger A
RA
Department of Medicine, Duke University and Durham VA Medical Centers, Box 3913, Durham, NC 27710, USA. lidd1001@mc.duke.edu
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004789:Enzyme Activation; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010195:Pancreatitis / Q000201:enzymology* / Q000235:genetics; D017354:Point Mutation; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen / Q000378:metabolism
D002352:Carrier Proteins; C486642:SPINK1 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen