Absence of the Major Zymogen Granule Membrane Protein, GP2, Does Not Affect Pancreatic Morphology or Secretion

Abstract

The majority of digestive enzymes in humans are produced in the pancreas where they are stored in zymogen granules before secretion into the intestine. GP2 is the major membrane protein present in zymogen granules of the exocrine pancreas. Numerous studies have shown that GP2 binds digestive enzymes such as amylase, thereby supporting a role in protein sorting to the zymogen granule. Other studies have suggested that GP2 is important in the formation of zymogen granules. A knock-out mouse was generated for GP2 to study the impact of the protein on pancreatic function. GP2-deficient mice displayed no gross signs of nutrient malabsorption such as weight loss, growth retardation, or diarrhea. Zymogen granules in the GP2 knock-out mice appeared normal on electron microscopy and contained the normal complement of proteins excluding GP2. Primary cultures of pancreatic acini appropriately responded to secretagogue stimulation with the secretion of digestive enzymes. The course of experimentally induced pancreatitis was also examined in the knock-out mice because proteins known to associate with GP2 have been found to possess a protective role. When GP2 knock-out mice were subjected to two different models of pancreatitis, no major differences were detected. In conclusion, GP2 is not essential for pancreatic exocrine secretion or zymogen granule formation. It is unlikely that GP2 serves a major intracellular role within the pancreatic acinar cell and may be functionally active after it is secreted from the pancreas.

Effects of Muclin (Dmbt1) deficiency on the gastrointestinal system

“…GP2 knockout mice have no spontaneous phenotype. During caerulein-induced pancreatitis, there was a transient increase in the number of apoptotic acinar cells in GP2 knockout cells, but otherwise the severity of pancreatitis was identical to WT mice (63). The other related knockout is of Itmap1 (also known as Cuzd1), which codes a CUB and ZP domaincontaining protein expressed in the exocrine pancreas.…”

Crohn’s disease specific pancreatic antibodies: clinical and pathophysiological challenges

“…However, much to the surprise of gastroenterologists, this hypothesis could not be supported by the pathophysological features of a GP2-deficient mouse model [63]. Therefore, research on GP2's urinary homologue, the Tamm-Horsfall protein (THP) or uromodulin, has also been considered important to reveal GP2's physiological functions [64,65].…”

<b>The broad distribution of GP2 in mucous glands and secretory pr</b><b>oducts </b>

“…Most researchers hypothesized the predominant functions of GP2 to be the formation of secretory granules or packaging and sorting of digestive enzymes. However, GP2 null mice displayed no detectable anomalies in either protein secretion or pancreatic acinar cell morphology (22). On the other hand, GP2 appeared as a candidate of transcytotic receptors specific for M cells of Peyer's patches (6,20), which are known to actively ingest macromolecules and microbes residing in the gut lumen.…”