Cl. Pin et al., The bHLH transcription factor Mist1 is required to maintain exocrine pancreas cell organization and acinar cell identity, J CELL BIOL, 155(4), 2001, pp. 519-530
The pancreas is a complex organ that consists of separate endocrine and exo
crine cell compartments. Although great strides have been made in identifyi
ng regulatory factors responsible for endocrine pancreas formation, the mol
ecular regulatory circuits that control exocrine pancreas properties are ju
st beginning to be elucidated. In an effort to identify genes involved in e
xocrine pancreas function, we have examined Mist1, a basic helix-loop-helix
transcription factor expressed in pancreatic acinar cells. Mist1-null (Mis
t1(KO)) mice exhibit extensive disorganization of exocrine tissue and intra
cellular enzyme activation. The exocrine disorganization is accompanied by
increases in p8, Reg1/PSP, and PAP1/RegIII gene expression, mimicking the m
olecular changes observed in pancreatic injury. By 12 m, Mist1(KO) mice dev
elop lesions that contain cells coexpressing acinar and duct cell markers.
Analysis of the factors involved in cholecystokinin (CCK) signaling reveal
inappropriate levels of the CCK receptor A and the inositol-1,4,5-trisphosp
hate receptor 3, suggesting that a functional defect exists in the regulate
d exocytosis pathway of Mist1(KO) mice. Based on these observations, we pro
pose that Mist1(KO) mice represent a new genetic model for chronic pancreas
injury and that the Mist1 protein serves as a key regulator of acinar cell
function, stability, and identity.