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Phenotypes Associated with This Genotype
Genotype
MGI:3531547
Allelic
Composition
Pdx1tm1Ted/Pdx1+
Genetic
Background
involves: 129P2/OlaHsd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pdx1tm1Ted mutation (0 available); any Pdx1 mutation (15 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• islet isolation procedures generate very few islets (always <100) from heterozygotes compared with wild-type mice (almost always >200 islets)
• isolated heterozygous islets appear fragmented and slightly smaller than wild-type
• in vivo, heterozygotes show a striking disruption of islet architecture and expansion of islet microvasculature at 3 months; however, even at 12 months, some heterozygous islets show no signs of damage or apoptosis
• in heterozygotes, islet number fails to increase with age and is ~50% less than wild-type by 12 months
• in heterozygotes, beta cell mass fails to increase with age and is ~50% less than wild-type by 12 months
• reduced beta cell mass is mirrored by a lower pancreatic insulin content in older mice and can be explained by a reduced number of functional islets, rather than a reduction in insulin stored in single beta cells
• heterozygotes display normal depolarization-evoked single-cell exocytosis and voltage-gated Ca2+ currents in beta cells
• however, isolated heterozygous islets and dispersed beta cells are significantly more susceptible to apoptosis at basal glucose concentrations than wild-type islets; no significant differences are noted at high glucose (25 mM) or Ca2+ stress
• perfused pancreata from heterozygous males display attenuated first-phase insulin secretion in response to a stepwise increase in glucose concentration from 5 mM to 20 mM glucose
• also, mutant pancreata show a reduced insulin release in response to 20 mM KCl; in the continued presence of 26 mM glucose, the large response to 20 mM arginine is also reduced
• notably, insulin secretion in perifusion or static incubation experiments in response to glucose and other secretagogues is similar in islets isolated from heterozygous mutants compared with wild-type littermates
• glucose sensing and islet Ca2+ responses are also normal in large, intact heterozygous mutant islets
• at 12 months, older heterozygotes exhibit infiltration of lymphocytes (some TUNEL-positive) within or around islets
• immunofluorescent localization of Ki67 nuclear antigen indicates proliferation of lymphocytes within these islets

homeostasis/metabolism
• perfused pancreata from heterozygous males display attenuated first-phase insulin secretion in response to a stepwise increase in glucose concentration from 5 mM to 20 mM glucose
• also, mutant pancreata show a reduced insulin release in response to 20 mM KCl; in the continued presence of 26 mM glucose, the large response to 20 mM arginine is also reduced
• notably, insulin secretion in perifusion or static incubation experiments in response to glucose and other secretagogues is similar in islets isolated from heterozygous mutants compared with wild-type littermates
• glucose sensing and islet Ca2+ responses are also normal in large, intact heterozygous mutant islets
• heterozygous mutant males exhibit significantly elevated blood glucose concentrations relative to wild-type males
• notably, heterozygous females display an attenuated increase in blood glucose levels relative to wild-type
• heterozygotes exhibit a decline in glucose tolerance with increasing age (J:82969)

immune system
• at 12 months, older heterozygotes exhibit infiltration of lymphocytes (some TUNEL-positive) within or around islets
• immunofluorescent localization of Ki67 nuclear antigen indicates proliferation of lymphocytes within these islets


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
04/19/2016
MGI 6.03
The Jackson Laboratory