Analysis Tools|
Allele Symbol Allele Name Allele ID |
Pdx1+ wild type MGI:2152758 |
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| Summary |
22 genotypes
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Data Sources
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• isolated heterozygous islets are significantly more susceptible to apoptosis at basal glucose concentrations than wild-type islets
• however, no significant differences are noted at high glucose (25 mM) or Ca2+ stress
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• dispersed beta cells are significantly more susceptible to apoptosis at basal glucose concentrations than wild-type islets
• however, no significant differences are noted at high glucose (25 mM) or Ca2+ stress
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• isolated heterozygous islets are significantly more susceptible to apoptosis at basal glucose concentrations than wild-type islets
• however, no significant differences are noted at high glucose (25 mM) or Ca2+ stress
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• dispersed beta cells are significantly more susceptible to apoptosis at basal glucose concentrations than wild-type islets
• however, no significant differences are noted at high glucose (25 mM) or Ca2+ stress
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• 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
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• 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
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• 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
• 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
• insulin secretion in perfusion 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 normal in large, intact heterozygous mutant islets
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• 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
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• 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
• 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
• insulin secretion in perfusion 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 normal in large, intact heterozygous mutant islets
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• 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
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• heterozygotes exhibit a decline in glucose tolerance with increasing age
(J:82969)
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• 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
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| maturity-onset diabetes of the young | DOID:0050524 |
OMIM:PS125850 |
J:48516 , J:82969 | |
| maturity-onset diabetes of the young type 4 | DOID:0111103 |
OMIM:606392 |
J:82969 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are phenotypically indistinguishable from wild-type and expression of the reporter faithfully reproduces the known expression pattern of Pdx1
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• heterozygotes display partially impaired glucose tolerance compared to wild-type mice; doxycycline treatment has no effect
(J:79206)
• heterozygotes display partially impaired early response to glucose challenge compared to wild-type mice; ability to recover after glucose challenge is impaired
(J:101742)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• heterozygotes display a normal fasting blood glucose and pancreatic insulin content relative to wild-type mice
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• heterozygotes show a 29% increase in pancreatic glucagon content relative to wild-type mice
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• perfused pancreata of heterozygotes secrete ~45% less insulin when stimulated with 16.7 mM glucose; the Km for insulin release is similar to that of wild-type mice
• also, perfused pancreata show a significantly reduced insulin release in response to 20 mM KCl (66%) and to 10 mM 2-ketoisocaproate (KIC; 61%)
• insulin secretion in response to 20 mM arginine is unchanged; the response to 10 nM glucagon-like peptide-1 is only slightly increased
• reduced insulin secretory responses to glucose, KIC, and KCl, as well as reduced generation of NAD(P)H, suggest mitochondrial dysfunction and/or abnormal mobilization of Ca2+
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• both heterozygous males and females display impaired glucose clearance after i.p. glucose administration; males are more affected than females
• impaired glucose tolerance is noted as early as 8 weeks and becomes more pronounced with increasing age (16-25 weeks)
• notably, 30% of male and 20% of female heterozygotes exhibit normal glucose tolerance; however, their plasma insulin levels are reduced to levels similar to those found in heterozygotes with impaired glucose tolerance
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• heterozygotes show a 29% increase in pancreatic glucagon content relative to wild-type mice
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• mutant islets show a marked (55%) but variable reduction in SLC2A2 expression relative to wild-type islets; in contrast, glucokinase expression remains unchanged
• however, at 16-18-weeks, heterozygotes show normal islet morphology and a normal ratio of beta to alpha or delta cells
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• at 25-40 weeks, heterozygotes show a 32% reduction in pancreatic islet amyloid polypeptide (IAPP) content relative to wild-type mice
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• perfused pancreata of heterozygotes secrete ~45% less insulin when stimulated with 16.7 mM glucose; the Km for insulin release is similar to that of wild-type mice
• also, perfused pancreata show a significantly reduced insulin release in response to 20 mM KCl (66%) and to 10 mM 2-ketoisocaproate (KIC; 61%)
• insulin secretion in response to 20 mM arginine is unchanged; the response to 10 nM glucagon-like peptide-1 is only slightly increased
• reduced insulin secretory responses to glucose, KIC, and KCl, as well as reduced generation of NAD(P)H, suggest mitochondrial dysfunction and/or abnormal mobilization of Ca2+
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• in addition, heterozygotes exhibit reduced insulin response to KIC, suggesting impaired mitochondrial metabolism and/or K+ATP channel-dependent stimulus-secretion coupling
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• heterozygous islets display a 30% reduction in NAD(P)H generation in response to 20 mM glucose
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• beta cell size is normal
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• mice exhibit an increase in the number of small islets with a decrease in medium and large sized islets compared with wild-type mice
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• beta cells exhibit increased endoplasmic reticulum stress that results in apoptosis unlike in wild-type mice
• beta cell replication and apoptosis are increased compared to in wild-type mice
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• mice exhibit beta cell apoptosis unlike in wild-type mice
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• in response to glucose in mice and isolated cells
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• in response to glucose in mice and isolated cells
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• mice exhibit beta cell apoptosis unlike in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 8-11 weeks of age, mice show severely impaired glucose clearance compared to wild-type
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• islets contain higher numbers of pancreatic polypeptide (PP)-producing cells compared to wild-type mice
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• islets contain higher numbers of glucagon-producing cells compared to wild-type mice
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• glucagon-producing cells are often intermixed with beta cells, rather than being peripherally located as in wild-type
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• at 10 weeks of age, mice have higher glucose levels than wild-type
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• levels are significantly decreased at 10 weeks
• at 8-11 weeks, plasma insulin is low 15 minutes after glucose challenge, with an overall smaller and delayed increase compared to controls
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• at 8-11 weeks of age, mice have severely impaired glucose clearance compared to conrol littermates; levels are >600 mg/dl glucose in many animals
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• insulin levels are lower than wild-type for at least 2 hours after administration of glucose
• insulin-to-glucose ratios are at about three times lower than controls 15 minutes into glucose tolerance tests
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• insulin levels are lower than wild-type for at least 2 hours after administration of glucose
• insulin-to-glucose ratios are at about three times lower than controls 15 minutes into glucose tolerance tests
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• mice have elevated blood glucose levels for at least 2 hours after glucose administration averaging around 350 mg/dl
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Reduction in Ngn3+ pancreatic endocrine progenitor cells in Pdx1tm1.1Stof/Pdx1+ and Pdx1tm1.1Stof/Pdx1tm1.1Stof mice
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• at E17.5, beta cells occupy less pancreatic area than in wild-type mice
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• at E19.5, apoptosis of Ngn3+ endocrine progenitor cells is increased compared to in wild-type mice
• however, the number of Ngn3+ endocrine progenitor cells at E17.5 is normal
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• unlike similarly treated wild-type mice, glucose-stimulated male mice fail to exhibit an increase in plasma insulin levels while female mice exhibit reduced fasting insulin levels
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• at 3 to 4 weeks, male mice are glucose intolerant unlike wild-type mice
• however, female mice exhibit normal glucose tolerance at 3 to 4 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit a decrease in median survival time which is approximately 2 months of age
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• mice develop invasive pancreatic ductal adenocarcinoma
• however, mice show negligible metastasis to distant organs
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• mice develop classical PanIN lesions that progress to invasive carcinoma
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• mice develop invasive pancreatic ductal adenocarcinoma
• however, mice show negligible metastasis to distant organs
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• mice develop classical PanIN lesions that progress to invasive carcinoma
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:248550 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit a decrease in median survival time which is approximately 4.5 months of age
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• mice develop invasive pancreatic ductal adenocarcinoma
• however, mice show negligible metastasis to distant organs with only 2 mice showing liver metastasis
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• both low and high grade PanIN lesions are seen at 2-3 months of age, but by 6 months, invasive carcinoma is present
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• mice develop invasive pancreatic ductal adenocarcinoma
• however, mice show negligible metastasis to distant organs with only 2 mice showing liver metastasis
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• both low and high grade PanIN lesions are seen at 2-3 months of age, but by 6 months, invasive carcinoma is present
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:248550 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• fewer cells are induced to produce glucagons than in Pdx1tm1Macd/Pdx1+ Tg(tetO-Neurog3)8Ggu mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• these mutants fail to exhibit an adaptive islet hyperplastic response to insulin resistance; instead, pancreatic beta cell mass is reduced, and islets appear small with scattered non-beta cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit an increase in the glucagon to insulin cell ratio as in Pdx1tm1Cvw heterozygotes
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• as in Pdx1tm1Cvw heterozygotes
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• as in Pdx1tm1Cvw heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• beta cell mass and the distribution of islet size are normalized unlike in either single heterozygote
• mice do not exhibit beta cell apoptosis unlike either single heterozygote
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• beta cell size is decreased compared to in wild-type mice or either single heterozygote
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• endoplasmic reticulum stress is reduced compared to in Pdx1tm1Cvw heterozygote
• beta cell replication is increased compared to in wild-type mice
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• glucose-stimulated insulin secretion is reduced compared to in wild-type mice but not as severely as in Pdx1tm1Cvw heterozygote
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• glucose-stimulated insulin secretion is reduced compared to in wild-type mice but not as severely as in Pdx1tm1Cvw heterozygote
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• compared with Pdx1tm1Cvw heterozygote
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• epithelial to mesenchyme transition is induced in the pancreas
• mice exhibit precocious endocrine differentiation, converting nearly all pancreatic cells to glucagon producing cells after E11.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit precocious endocrine differentiation, converting 1.8-fold more pancreatic cells to glucagon producing, immature alpha cells at E11.5 than in Pdx1tm1Macd heterozygotes
• however, this conversion is not sustained later in development as E18.5, only rare glucagons producing cells are found
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• when treated with doxycycline until E12.5, mice exhibit normal no ectopic mass at the pyloric-duodenum junction
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• at E16.5, mice exhibit a large mass at the pyloric junction between the stomach and duodenum unlike in control mice
• at E16.5, mice exhibit many ectopic duct-like structures unlike in control mice
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• at 6 weeks, in mice treated with doxycycline until E12.5
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• at 6 weeks, mice treated with doxycycline until E12.5 exhibit a massive expansion of ductal tissues compared to in control mice
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• at E16.5, mice exhibit hyperplastic stomach epithelium and mesenchyme
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• hyperplastic at E16.5
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• when treated with doxycycline until E12.5, endocrine cells are replaced with ductal cells unlike in control mice
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• at 6 weeks, in mice treated with doxycycline until E12.5
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• at 6 weeks, mice treated with doxycycline until E12.5 exhibit a massive expansion of ductal tissues compared to in control mice
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• at 6 weeks, mature endocrine cells are nearly absent in mice treated with doxycycline until E12.5 unlike in control mice
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• at E10.5, the remnant of the dorsal and ventral pancreatic bud is fused to the gut tube unlike in control mice
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• at E16.5, only a pancreatic remnant remains
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| N |
• liver bud development and biliary epithelium are normal
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• at 6 weeks, mice treated with doxycycline until E12.5 exhibit a massive expansion of ductal tissues compared to in control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• dynamic and AMPK-independent cyst formation in late, but not early, stage pancreas explants treated with 1NMPP1
• pancreatic cysts induced by treatment with 1NMPP1 evolve into precancerous-like lesions without loss of cell polarity
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• increased epithelial cell proliferation accompanies pancreatic cyst formation in 1NMPP1-treated pancreatic explants
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• dynamic and AMPK-independent cyst formation in late, but not early, stage pancreas explants treated with 1NMPP1
• pancreatic cysts induced by treatment with 1NMPP1 evolve into precancerous-like lesions without loss of cell polarity
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• disrupted architecture, inappropriate cell types interspersed with beta cells
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• 9-10 weeks
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• onset between 9-10 weeks, progresses to overt diabetes
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| type 2 diabetes mellitus | DOID:9352 |
OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036 |
J:75811 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• islet cell hyperplasia becomes prominent by 40 weeks of age and persists until late in life
• islet mass increases 6- to 8-fold by 21 months of age
• this increase is due only to an increase in beta-cell mass
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• insulin levels are lower than wild-type for at least 2 hours after administration of glucose
• insulin-to-glucose ratios are at least three times lower than controls 15 minutes into glucose tolerance tests
• insulin secretion is also significantly decreased during in situ pancreas infusion with either 5.6 mM glucose or 20mM arginine
• there is less insulin per mg of pancreatic protein in mice 31 to 47 weeks in age
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• insulin levels are lower than wild-type for at least 2 hours after administration of glucose
• insulin-to-glucose ratios are at least three times lower than controls 15 minutes into glucose tolerance tests
• insulin secretion is also significantly decreased during in situ pancreas infusion with either 5.6 mM glucose or 20mM arginine
• there is less insulin per mg of pancreatic protein in mice 31 to 47 weeks in age
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• fasting glucose levels rise with age so that by 48 weeks of age half of these mice have a blood glucose level higher than 150mg/dl
• mean glucose levels are significantly higher than controls by 32 weeks of age
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• insulin levels are reduced with age
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• mice have extremely elevated blood glucose levels for at least 2 hours after glucose administration averaging around 475 mg/dl
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 03/18/2025 MGI 6.24 |
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