Phenotypes for Foxm1 Tg(Pdx1-cre)89.1Dam MGI:5638149 MGI Mouse

abnormal glucose homeostasis ( J:111026 )

• 13% of males are diabetic at 9 weeks of age

• total pancreatic insulin content is decreased in males at 6 and 9 weeks of age, and is only 30% of control levels at 9 weeks

impaired glucose tolerance ( J:111026 )

• 29% of males develop impaired glucose tolerance at 6 weeks of age, as indicated by elevated blood glucose levels at 30, 60, 90, and 120 minutes of an intraperitoneal glucose tolerance test

• 53% of males are glucose intolerant by 9 weeks of age

• females, however, exhibit normal intraperitoneal glucose tolerance test

pancreas necrosis ( J:111026 )

• exocrine tissue from diabetic males shows many enlarged cells undergoing lysis and losing membrane integrity, signs of cellular necrosis

decreased pancreatic beta cell proliferation ( J:111026 )

• decrease in beta-cell proliferation at 4, 6, and 9 weeks of age

abnormal exocrine pancreas morphology ( J:111026 )

• in some glucose intolerant males at 6 weeks of age, the exocrine nuclei are enlarged and the islets look smaller

• in 9 week old diabetic males, cysts are present in the exocrine pancreas

• orientation of exocrine cells is irregular and nuclei of disorganized exocrine cells are enlarged in 9 week old diabetic males

abnormal pancreatic islet morphology ( J:111026 )

• at 9 weeks of age, pancreas from diabetic males shows alteration in islet architecture, with a decrease in insulin-producing cells, an increase in alpha-cells and scattering of alpha-cells throughout the islets rather than at the periphery

• pancreas from males with impaired glucose tolerance or diabetes shows an increase in intra-islet keratin-positive cells, suggesting that islets contain cells with a ductal phenotype

increased pancreatic alpha cell number ( J:111026 )

• at 9 weeks of age, pancreas from diabetic males shows an increase in alpha-cells

abnormal pancreatic beta cell morphology ( J:111026 )

• although the average beta-cell size per pancreas is the same as in controls at 9 weeks, the average beta-cell size per islet is variable, with some islets composed mainly of beta-cells that are much larger than the average and others composed of beta-cells less than 60 um², indicating that some beta-cells are undergoing hypertrophy and others are dying

decreased pancreatic beta cell mass ( J:111026 )

• decrease in beta-cell mass is seen at 4, 6, and 9 weeks of age compared to controls: mice show an initial increase in beta-cell mass from P1 to 4 weeks of age and thereafter remain the same or slightly decreased compared to controls which show continued beta cell mass increase from P1 to 9 weeks

• beta-cell mass of males is only about 30% of controls at 9 weeks of age

• females show an approximate 20% decrease in beta-cell mass at 9 weeks of age

decreased pancreatic beta cell number ( J:111026 )

• pancreas from males show a gradual loss of insulin-producing cells

small pancreatic islets ( J:111026 )

• islet size in both males and females is smaller than controls at 9 weeks of age

decreased pancreas weight ( J:111026 )

• whole pancreatic wet weights are slightly but significantly lower in males at 9 weeks of age

pancreas cyst ( J:111026 )

• in 9 week old diabetic males, cysts are present in the exocrine pancreas; cysts are negative for oil red O staining indicating that they are not adipose accumulations and are most likely due to necrotic cell death

abnormal insulin secretion ( J:111026 )