Phenotypes Associated with This Genotype

Genotype
MGI:6277073

• Allelic Composition: Ccpg1^{tm1a(EUCOMM)Hmgu}/Ccpg1^{tm1a(EUCOMM)Hmgu}
• Genetic Background: C57BL/6N-Ccpg1^{tm1a(EUCOMM)Hmgu}
• Cell Lines: HEPD0725_5_F09

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

endocrine/exocrine glands

abnormal gastric chief cell morphology ( J:256708 )

• chief cells of the adult gastric epithelium exhibit loss of polarity, similar to that observed in pancreatic acinar cells

abnormal exocrine pancreas physiology ( J:256708 )

• at 6 weeks of age, exocrine pancreata exhibit a proteostasis defect in acinar cells

• however, no significant reductions in plasma amylase levels or mRNA levels of key differentiation markers of the pancreatic exocrine lineage are observed

abnormal pancreatic acinar cell physiology ( J:256708 )

• a significant fraction of Ki67+ cells are detected in the normally quiescent acinar cell population at 20 weeks of age, indicating compensatory proliferation of acinar cells in response to injury

abnormal pancreas morphology ( J:256708 )

• at 6 weeks of age, pancreatic tissues appear whitened and opaque, unlike in wild-type controls

pancreas necrosis ( J:256708 )

• at 40 weeks of age, dead pancreatic acinar cells are often observed within the center of inflammatory infiltrates

abnormal pancreatic acinar cell morphology ( J:256708 )

• young adult pancreatic acinar cells accumulate endoplasmic reticulum (ER) that is laden with insoluble zymogen protein

• acinar ER-synthesized enzymes and ER luminal chaperones accumulate in insoluble aggregates

• condensed or heterogeneously sized inclusions are trapped within the lumen; many supernumerary inclusions are in fact intracisternal granule-like structures

pancreas inflammation ( J:256708 )

• at 40 weeks of age, pancreata show numerous sporadic inflammatory infiltrates, esp. around necrotic cells and in the vicinity of ducts and blood vessels

digestive/alimentary system

abnormal pancreatic acinar cell morphology ( J:256708 )

• young adult pancreatic acinar cells accumulate endoplasmic reticulum (ER) that is laden with insoluble zymogen protein

• acinar ER-synthesized enzymes and ER luminal chaperones accumulate in insoluble aggregates

• condensed or heterogeneously sized inclusions are trapped within the lumen; many supernumerary inclusions are in fact intracisternal granule-like structures

abnormal gastric chief cell morphology ( J:256708 )

• chief cells of the adult gastric epithelium exhibit loss of polarity, similar to that observed in pancreatic acinar cells

abnormal exocrine pancreas physiology ( J:256708 )

• at 6 weeks of age, exocrine pancreata exhibit a proteostasis defect in acinar cells

• however, no significant reductions in plasma amylase levels or mRNA levels of key differentiation markers of the pancreatic exocrine lineage are observed

abnormal pancreatic acinar cell physiology ( J:256708 )

• a significant fraction of Ki67+ cells are detected in the normally quiescent acinar cell population at 20 weeks of age, indicating compensatory proliferation of acinar cells in response to injury

cellular

abnormal endoplasmic reticulum morphology ( J:256708 )

• distension and disrupted cellular distribution of the rough ER within the pancreatic acinar cells

abnormal reticulophagy ( J:256708 )

• loss of ER-phagy capacity, the selective sequestration of ER material into autophagosomes, in pancreatic acinar cells

pancreas necrosis ( J:256708 )

• at 40 weeks of age, dead pancreatic acinar cells are often observed within the center of inflammatory infiltrates

increased endoplasmic reticulum stress ( J:256708 )

• loss of ER proteostasis results in accumulated and distended ER within pancreatic acinar cells and hyperactivation of the unfolded protein response (UPR) by 6 weeks of age

• upregulation of molecular markers of ER stress, consistent with a loss of ER-phagic regulation of ER homeostasis and tissue injury of the exocrine pancreas

homeostasis/metabolism

abnormal reticulophagy ( J:256708 )

• loss of ER-phagy capacity, the selective sequestration of ER material into autophagosomes, in pancreatic acinar cells

immune system

pancreas inflammation ( J:256708 )

• at 40 weeks of age, pancreata show numerous sporadic inflammatory infiltrates, esp. around necrotic cells and in the vicinity of ducts and blood vessels