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Phenotypes Associated with This Genotype
Genotype
MGI:5638149
Allelic
Composition
Foxm1tm1Rhc/Foxm1tm1Rhc
Tg(Pdx1-cre)89.1Dam/0
Genetic
Background
involves: 129X1/SvJ * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxm1tm1Rhc mutation (0 available); any Foxm1 mutation (6 available)
Tg(Pdx1-cre)89.1Dam mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• 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
• 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

endocrine/exocrine glands
• decrease in beta-cell proliferation at 4, 6, and 9 weeks of age
• 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
• 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
• at 9 weeks of age, pancreas from diabetic males shows an increase in alpha-cells
• 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
• 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
• pancreas from males show a gradual loss of insulin-producing cells
• islet size in both males and females is smaller than controls at 9 weeks of age
• whole pancreatic wet weights are slightly but significantly lower in males at 9 weeks of age
• 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
• exocrine tissue from diabetic males shows many enlarged cells undergoing lysis and losing membrane integrity, signs of cellular necrosis
• 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

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

digestive/alimentary system
• 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


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
11/13/2018
MGI 6.13
The Jackson Laboratory