Phenotypes associated with this allele

• Allele Symbol: Tg(Pdx1-cre)1Herr
• Allele Name: transgene insertion 1, Pedro Luis Herrera
• Allele ID: MGI:2387562
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Myc^tm2.1Atp/Myc^tm2.1Atp Tg(Pdx1-cre)1Herr/0	involves: 129P2/OlaHsd * C57BL/6J * CBA/J	MGI:4412367
cn2	Clec16a^tm1.1Hhak/Clec16a^tm1.1Hhak Tg(Pdx1-cre)1Herr/0	involves: C57BL/6 * C57BL/6J * CBA/J * SJL	MGI:5766645

Genotype
MGI:4412367

cn1

• Allelic Composition: Myc^tm2.1Atp/Myc^tm2.1Atp; Tg(Pdx1-cre)1Herr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * CBA/J

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

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:146087 )

N • at birth and 2 months, pancreatic contents of insulin and glucagon are similar to that of controls; islet architecture and function are normal

abnormal pancreas morphology ( J:146087 )

• in newborns, diminished surface occupied by exocrine pancreas is composed of poorly polarized acinar cells

• at 2 months, histology is grossly normal, but adipocytes accumulate in the parenchyma

• in 10 month old animals, adipose tissue is abundant; however pancreas weight is still reduced by 31%

• adipose replacement of acinar cells is gradual with 2 intermediate cells observed: acinar cells containing small lipid droplets and fat-laden cells containing zymogen but lacking other acinar markers; this suggests that acinar cells transdifferentiate into adipocytes in mature mutants

abnormal pancreatic acinus morphology ( J:146087 )

• loss of exocrine tissue affects 50% of the acinar mass

abnormal pancreatic acinar cell morphology ( J:146087 )

• acinar cells from newborns and adults have less amylase+ve and Cpa+ve zymogen granules than controls and are poorly polarized; in some pancreata, cellular localization of zymogen granules in adult cells is altered due to accumulation of lipid droplets

• some amylase containing zymogen granules are located within the thin cytoplasmic rim of adipocytes

• at 10 months, remaining acinar cells show similar dysmorphic traits to those in younger animals (see note above)

• adipose replacement of acinar cells is gradual with 2 intermediate cells observed: acinar cells containing small lipid droplets and fat-laden cells containing zymogen but lacking other acinar markers; this suggests that acinar cells transdifferentiate into adipocytes in mature mutants

absent pancreatic acinar cells ( J:146087 )

• in 10 month-old animals, acinar cells are totally absent in entire pancreatic lobes

abnormal pancreatic duct morphology ( J:146087 )

• arborization of exocrine tree in newborns is reduced to 51% of controls and to 17% in adults

• loss of exocrine tissue affects 70% of the ductal mass

abnormal pancreas development ( J:146087 )

• growth of main pancreatic axes is unaffected but secondary branches are less developed at E15.5 and in newborns

• at E12.5, pancreata contain less proliferating pHH3+/Pdx1+/amylase -ve progenitor cells than controls

abnormal pancreas size ( J:146087 )

decreased pancreas weight ( J:146087 )

• at 2 months, pancreas weight is reduced to 55% of control weight

pancreas hypoplasia ( J:146087 )

• pancreas is hypoplastic from E12.5 onward

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:146087 )

• at birth amylase activity in pancreatic extracts is 7% of controls, but recovers to 57% by 2 months of age; amylase acitivity per gram/pancreas is reduced 4-fold in newborns and partially recovered at 2 months

digestive/alimentary system

abnormal pancreatic acinus morphology ( J:146087 )

• loss of exocrine tissue affects 50% of the acinar mass

abnormal pancreatic acinar cell morphology ( J:146087 )

• acinar cells from newborns and adults have less amylase+ve and Cpa+ve zymogen granules than controls and are poorly polarized; in some pancreata, cellular localization of zymogen granules in adult cells is altered due to accumulation of lipid droplets

• some amylase containing zymogen granules are located within the thin cytoplasmic rim of adipocytes

• at 10 months, remaining acinar cells show similar dysmorphic traits to those in younger animals (see note above)

• adipose replacement of acinar cells is gradual with 2 intermediate cells observed: acinar cells containing small lipid droplets and fat-laden cells containing zymogen but lacking other acinar markers; this suggests that acinar cells transdifferentiate into adipocytes in mature mutants

absent pancreatic acinar cells ( J:146087 )

• in 10 month-old animals, acinar cells are totally absent in entire pancreatic lobes

abnormal pancreatic duct morphology ( J:146087 )

• arborization of exocrine tree in newborns is reduced to 51% of controls and to 17% in adults

• loss of exocrine tissue affects 70% of the ductal mass

Genotype
MGI:5766645

cn2

• Allelic Composition: Clec16a^tm1.1Hhak/Clec16a^tm1.1Hhak; Tg(Pdx1-cre)1Herr/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * CBA/J * SJL

homeostasis/metabolism

abnormal mitophagy ( J:214528 )

• accumulation of unhealthy mitochondria, coupled with dysregulation of the Nrdp1/Parkin pathway, suggests defective mitophagy/autophagy leading to impaired glucose-stimulated OCR and insulin secretion

decreased insulin secretion ( J:214528 )

• mice show reduced basal and blunted insulin release at 0 and 3 min after glucose administration in vivo and in isolated islets

• no differences in peripheral insulin sensitivity are observed

hyperglycemia ( J:214528 )

• mice exhibit hyperglycemia due to functional defects in beta cells

decreased oxygen consumption ( J:214528 )

• pancreatic islets show reduced glucose-stimulated oxygen consumption rate (OCR) as well as maximal OCR following FCCP treatment (to induce mitophagy) relative to wild-type islets

impaired glucose tolerance ( J:214528 )

• intraperitoneal glucose tolerance testing (IPGTT) revealed that mice are significantly hyperglycemic relative to controls

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:214528 )

N • no signs of exocrine pancreatic dysfunction, such as weight loss, steatorrhea, or abnormal acinar or ductal cell histology

N • no evidence of infiltrating lymphocytes into the pancreatic islets

N • normal islet architecture and beta cell mass

abnormal pancreatic alpha cell morphology ( J:214528 )

• pancreatic alpha cells exhibit rounded mitochondria with a severely disordered and amorphous structure

abnormal pancreatic beta cell morphology ( J:214528 )

• at 3 months, TEM revealed an accumulation of vacuolated structures, some containing partially degraded cytoplasmic material consistent with autophagic vacuoles, not observed in wild-type beta cells

• beta cells exhibit rounded mitochondria with a severely disordered and amorphous structure, including an increased number of distorted cristae and inclusions not observed in wild-type cells

• 3D EM reconstruction tomography showed accumulation of electron lucent vacuolated structures, including large interconnected vacuoles (likely dilated ER), and smaller spherical vacuoles (possibly endosomes)

abnormal pancreatic beta cell physiology ( J:214528 )

• mice show a significant increase in total pancreatic insulin content at age 12 weeks

decreased insulin secretion ( J:214528 )

• mice show reduced basal and blunted insulin release at 0 and 3 min after glucose administration in vivo and in isolated islets

• no differences in peripheral insulin sensitivity are observed

cellular

abnormal endoplasmic reticulum morphology ( J:214528 )

• pancreatic beta cells show age-dependent alterations in ER morphology, indicative of ER stress

abnormal mitochondrial morphology ( J:214528 )

• pancreatic beta cells exhibit rounded mitochondria with a severely disordered and amorphous structure, including an increased number of distorted cristae and inclusions not observed in wild-type cells

disorganized mitochondrial cristae ( J:214528 )

• distorted mitochondrial cristae in pancreatic beta cells

increased mitochondrial size ( J:214528 )

• increased mitochondrial mass in pancreatic islets, as shown by increased mtDNA levels and levels of the mitochondrial proteins succinate dehydrogenase A and mitochondrial complex IV subunit I

abnormal mitophagy ( J:214528 )

• accumulation of unhealthy mitochondria, coupled with dysregulation of the Nrdp1/Parkin pathway, suggests defective mitophagy/autophagy leading to impaired glucose-stimulated OCR and insulin secretion