Analysis Tools
liver/biliary system
| N |
• mice exhibit normal development of the gall bladder, collecting ducts, and common duct
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Allele Symbol Allele Name Allele ID |
Pdx1tm1Macd targeted mutation 1, Raymond J MacDonald MGI:2388676 |
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| Summary |
8 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal development of the gall bladder, collecting ducts, and common duct
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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 |
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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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• 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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• in doxycycline-treated mice there is an increase in glucagons-positive cells
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• there is a marked reduction in insulin in pancreata of doxycycline-treated mice; after withdrawal of doxycycline, insulin +ve cells are detected in islets of smaller islet-like cell clusters
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• 14 days after doxycycline withdrawal after 14 days of treatment resulted in a significant decrease in blood glucose levels with 4/5 mice becoming normoglycemic by 28 days
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• with doxycycline treatment for 21 day, adult rescue mice show a 4-fold increase in fasting blood glucose to diabetic levels
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• adult transgenic rescue animals treated with doxycycline for 14 days exhibit a defective response to glucose challenge compared to wild-type, non mutant transgenic, or untreated rescue mice
(J:79206)
• when adult mice are treated with doxycycline for 0, 7, 14, or 21 days, mice show an increased early glucose response within 7 days of start of treatment and ability to recover from glucose challenge is impaired compared to untreated transgenics where glucose levels recover to basal levels within 3 hours; by 14 days of doxycycline treatment, mice have diabetes
(J:101742)
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• after 14 or 28 days of dox treatment there are, still present, beta cells which lack insulin
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• after dox treatment for 14 days, there is a significant decrease in islet area compared to wild-type
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• pancreas of transgenic rescue newborn mice is 50% the size of a normal wild-type neonatal pancreas
• treatment of pregnant mice with doxycycline from the first day of pregnancy through parturition prevents formation of the pancreas in mice with the transgenic rescue genotype
• treatment on E11.5 arrests pancreatic development ~36 hours later; at birth the underdeveloped remnant consisted of a large and extended duct with several terminal, aborted, ductal buds with ducts lined with a single layer of primitive epithelial cells and with no acinar or islet tissue
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• in doxycycline-treated mice there is an increase in glucagons-positive cells
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• there is a marked reduction in insulin in pancreata of doxycycline-treated mice; after withdrawal of doxycycline, insulin +ve cells are detected in islets of smaller islet-like cell clusters
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• foci of duct proliferation are present in mice after 14 days of doxycycline treatment and become more prominent with continued treatment
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• transgenic mice gradually attain an impaired glucose tolerance response to glucose challenge
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• when dams are treated with doxycycline from conception through birth, only small epithelial remnants of the pancreas form; treatment at E7.5 or E8.5 results in the same phenotype
• doxycycline from E9.5 diminishes epithelial morphogenesis; treatement from E9.5 allows outgrowth of a linear epithelial tube with nascent invaginations representing initial primary branching
• treatment from E11.5 allows the formation of a larger crude duct-like structure with a few distal primary branches; treatement from E12.5 permits formation of extensive fine structure consisting of immature acini and associated small ductules
• with treatment from E12.5, pancreatic dorsal and ventral remnants composed of convoluted partially branched duct-like epithelium of columnar epithelium are present, and show a block at the stage of acinar cell formation
• examination of embryo ductal remnants from mice treated with dox from E11.5 show an absence of preacini; treatment from E12.5 results in a larger remnant with a smaller proportion of primitive duct; the epithelium is replaced by numerous eosinophilic clusters lacking ductal markers which are polarized, arranged around a central lumen and resemble immature acini
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• ~1/5 pups are born without a pancreas; rescue of pancreas formation is observed in ~80% of transgenic mice
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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 09/03/2024 MGI 6.24 |
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