Analysis Tools|
Allele Symbol Allele Name Allele ID |
Tg(Pdx1-cre)6Tuv transgene insertion 6, David A Tuveson MGI:3032531 |
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| Summary |
67 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• beta cells, identified by immunostaining for insulin, occupied a greater proportional area of pancreas sections from adult mice bearing both the conditional Neurog3 knock-in and the embryonically expressed (E9.5-E12.5) pancreatic progenitor cell-specific cre recombinase transgene than in sections from control mice with only the conditional allele (highly significant at p = 0.007 (<= 0.01) by Student's unpaired t test).
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop gastric adenocarcinomas with a median tumor-free survival of 9.4 months but do not develop distant metastases
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• mice develop gastric adenocarcinomas with a median tumor-free survival of 9.4 months but do not develop distant metastases
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most common cause of death is duodenal obstruction, followed by gastric outlet obstruction
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• 36% of mice develop duodenal adenocarcinomas
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• 84% of mice develop spontaneous tumors in the glandular stomach with a median tumor-free survival of 8 months
• gastric tumors resemble diffuse-type gastric adenocarcinomas, are E-cadherin-negative, and are invasive into the muscle layers and regional lymph nodes
• intramucosal adenocarcinomas with signet ring cell feature is seen in 2 of 4 mice at 6 months of age
• gastric premalignant lesions such as atrophic gastritis, metaplasia or dysplasia are not seen at 4 and 5 months of age
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• 3 of 21 mice with gastric adenocarcinomas develop lung metastases
• metastatic lesions have similar cytologic features to primary gastric tumors
• 8% of mice exhibit adenocarcinomas in the pancreas, most likely due to invasion of the primary duodenal or gastric adenocarcinomas
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• 24% of mice develop forestomach squamous cell carcinomas
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• 36% of mice develop duodenal adenocarcinomas
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• 84% of mice develop spontaneous tumors in the glandular stomach with a median tumor-free survival of 8 months
• gastric tumors resemble diffuse-type gastric adenocarcinomas, are E-cadherin-negative, and are invasive into the muscle layers and regional lymph nodes
• intramucosal adenocarcinomas with signet ring cell feature is seen in 2 of 4 mice at 6 months of age
• gastric premalignant lesions such as atrophic gastritis, metaplasia or dysplasia are not seen at 4 and 5 months of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| stomach cancer | DOID:10534 |
OMIM:613659 |
J:212549 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit a similar overall pancreatic tumor burden as KPCT (Krastm4Tyj/Kras+ Trp53tm2Tyj/Trp53+ Tg(Pdx1-cre)6Tuv/0 Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor+) mice
• pancreas contains PanINs and adenocarcinoma that are similar to pancreatic ductal adenocarcinoma (PDAC) in KPCT mice
• only 3 of 14 mice develop metastases, with only half of mice showing peritoneal disseminated tumor cells
• cancer cells exhibit a higher mitotic index than KPCT mice
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• pancreas contains PanINs and adenocarcinoma that are similar to PDAC in KPCT mice
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• mice exhibit a shorter survival than KPCT mice
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• mice exhibit a similar overall pancreatic tumor burden as KPCT (Krastm4Tyj/Kras+ Trp53tm2Tyj/Trp53+ Tg(Pdx1-cre)6Tuv/0 Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor+) mice
• pancreas contains PanINs and adenocarcinoma that are similar to pancreatic ductal adenocarcinoma (PDAC) in KPCT mice
• only 3 of 14 mice develop metastases, with only half of mice showing peritoneal disseminated tumor cells
• cancer cells exhibit a higher mitotic index than KPCT mice
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• pancreas contains PanINs and adenocarcinoma that are similar to PDAC in KPCT mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• pancreas contains PanINs and adenocarcinoma
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• pancreas contains PanINs and adenocarcinoma
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• pancreas contains PanINs and adenocarcinoma
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• pancreas contains PanINs and adenocarcinoma
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• most mice develop metastases which are numerous and widespread in many different sites, including the lymph nodes, diaphragm, lungs, and liver
• all mice exhibit peritoneal disseminated tumor cells
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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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• as in mice lacking the BRF1 knock-in
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• as in mice lacking the BRF1 knock-in
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• tRNA levels are increased in the pancreas
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• as in mice lacking the BRF1 knock-in
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• tRNA levels are increased in the pancreas
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• not as severe as in mice wild-type for Cd9 or homozygous for a conditional allele
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• as severe as in mice wild-type for Cd9
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• at 8 weeks, more severe than in mice heterozygous for the Cd9 conditional allele
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• at 8 weeks, more severe than in mice heterozygous for the Cd9 conditional allele
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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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• not as severe as in mice wild-type for Cd9 or homozygous for a conditional allele
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• at 8 weeks, not as severe as in mice wild-type for Cd9 or homozygous for a conditional allele
• increased tumor weight compared to in mice homozygous for a conditional allele
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• compared to in mice homozygous for a conditional allele
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• at 8 weeks, not as severe as in mice wild-type for Cd9 or homozygous for a conditional allele
• increased tumor weight compared to in mice homozygous for a conditional allele
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all mice die by 30 weeks of age
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• at 8 weeks
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• at 8 weeks
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• at 8 weeks
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• at 8 weeks
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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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• mice do not survive beyond P21
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• mice develop highly aggressive adenocarcinoma with a ductal cell phenotype and inflammation resembling human pancreatic ductal adenocarcinoma within a short period (5 and 10 days after birth) and die within 3 weeks
• at P16, pancreatic ductal adenocarcinoma progresses to occupy the whole pancreas and to invade the muscular wall of the duodenum
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• PanIN-3 are detected in the pancreas with inflammation at P3 and P4
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• mice develop highly aggressive adenocarcinoma with a ductal cell phenotype and inflammation resembling human pancreatic ductal adenocarcinoma within a short period (5 and 10 days after birth) and die within 3 weeks
• at P16, pancreatic ductal adenocarcinoma progresses to occupy the whole pancreas and to invade the muscular wall of the duodenum
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• PanIN-3 are detected in the pancreas with inflammation at P3 and P4
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• invasive features of pancreatic ductal adenocarcinoma are seen containing acinoductal metaplasia at P5-P10
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• hemorrhagic ascites are seen by P16
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:214846 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit rapid development of pancreatic tumors within 8 weeks with features typical of human pancreatic adenocarcinoma
• tumors treated with ibrutinib show a reduction in proliferation rate and tumor fibrosis, inhibition of mast cell degranulation, and reduction in CD11b+ and F4/80+ macrophages and mice show increased survival
• mice treated with both ibrutinib and gemcitabine show extended survival compared to treatment with gemcitabine alone
• mice treated with a daily injection of cromolyn, a blocker of mast cell degranulation and inflammogen release, starting at 8 weeks of age show a reduction in F4/80+ cells and CD11b+ cells in the tumor stroma
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• mice exhibit rapid development of pancreatic tumors within 8 weeks with features typical of human pancreatic adenocarcinoma
• tumors treated with ibrutinib show a reduction in proliferation rate and tumor fibrosis, inhibition of mast cell degranulation, and reduction in CD11b+ and F4/80+ macrophages and mice show increased survival
• mice treated with both ibrutinib and gemcitabine show extended survival compared to treatment with gemcitabine alone
• mice treated with a daily injection of cromolyn, a blocker of mast cell degranulation and inflammogen release, starting at 8 weeks of age show a reduction in F4/80+ cells and CD11b+ cells in the tumor stroma
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:220300 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduced glutamate uptake and intracellular levels in organoids derived from tumor initiating cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• after 5 days in culture, pancreatic explants exhibit irregular branching and disorganization with increased proliferation, pseudostratification, nuclear crowding and elongation resembling precancerous lesions
• however, no cysts develop
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• after 5 days in culture, pancreatic explants exhibit irregular branching with increased proliferation
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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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• about 18% of assessable tumor cases develop an acinar-cell carcinoma component of pancreatic tumors
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• high penetrance (29 of 30 mutants) of pancreatic ductal adenocarcinomas
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• average survival time is 84 days, with a range of 48-110 days
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• about 18% of assessable tumor cases develop an acinar-cell carcinoma component of pancreatic tumors
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• high penetrance (29 of 30 mutants) of pancreatic ductal adenocarcinomas
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:166678 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• pancreatic insufficiency is occasionally observed in mutants
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• pancreatic insufficiency is occasionally observed in mutants
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• premature death before 600 days of age due to lymphoid malignancies and sarcomas
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• mutants develop lymphoid malignancies
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• pancreatic insufficiency; spectrum of anomalies are seen from isolated paucity of the islets of Langerhans to complete fibro-inflammatory or cystic degeneration of both the endocrine and exocrine pancreas
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• pancreata from 6 day old mutants exhibits an increase in apoptotic cells compared to controls
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• pancreatic insufficiency; spectrum of anomalies are seen from isolated paucity of the islets of Langerhans to complete fibro-inflammatory or cystic degeneration of both the endocrine and exocrine pancreas
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• mutants not succumbing to pancreatic insufficiency later develop pancreatic ductal adenocarcinomas with a moderate latency and incomplete penetrance (6 of 32 mutants)
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• mutants exhibit shortened pancreatic ductal adenocarcinoma-free survival
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• mutants not succumbing to pancreatic insufficiency later develop pancreatic ductal adenocarcinomas with a moderate latency and incomplete penetrance (6 of 32 mutants)
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• pancreata from 6 day old mutants exhibits an increase in apoptotic cells compared to controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• small fraction of mutants develop pancreatic insufficiency
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• small fraction of mutants develop pancreatic insufficiency
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• premature death in the small fraction of mutants with pancreatic insufficiency
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die within 200 days after birth, showing symptoms to that seen in wasting disease
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• mice develop pancreatic acinar cell dysplasia by 22 weeks without PanIN formation
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• pancreatic ductal system and ductal cells are atrophic by 22 weeks of age
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• mice develop pancreatic acinar cell dysplasia by 22 weeks without PanIN formation
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• pancreatic ductal system and ductal cells are atrophic by 22 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants become moribund before they develop large tumors
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• mice develop pancreatic tumors as early as 14 days post partum
• all mice develop pancreatic neoplasms in less than 5 months
• 43% of mutants develop only ductal lesions, 46% of mutants have both ductal lesions and poorly differentiated carcinomas, and 11% of mutants exhibit only poorly differentiated adenocarcinomas
• 40-50 day old mutants with palpable pancreatic neoplasms treated with doxycycline for 7 days show cancer regression, however tumor-associated stroma does not remodel/regress
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• 43% of mutants develop only ductal lesions that include pancreatic intraepithelial neoplasia (PanINs) and invasive pancreatic ductal adenocarcinomas (PDACs) with sporadic metastasis to the liver
• 11% of mutants exhibit exclusively poorly differentiated adenocarcinomas that can metastasize to the liver, diaphragm, and lung
• 46% of mutants have both ductal lesions and poorly differentiated carcinomas, with a few mutants having moderately differentiated lesions that have an acinar-like appearance
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• 43% of mutants develop only ductal lesions that include pancreatic intraepithelial neoplasia (PanINs) and invasive pancreatic ductal adenocarcinoma (PDACs) with sporadic metastasis to the liver
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• pancreatic ductal adenocarcinomas metastasize to the liver, diaphragm, and lung
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• mice develop pancreatic tumors as early as 14 days post partum
• all mice develop pancreatic neoplasms in less than 5 months
• 43% of mutants develop only ductal lesions, 46% of mutants have both ductal lesions and poorly differentiated carcinomas, and 11% of mutants exhibit only poorly differentiated adenocarcinomas
• 40-50 day old mutants with palpable pancreatic neoplasms treated with doxycycline for 7 days show cancer regression, however tumor-associated stroma does not remodel/regress
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• 43% of mutants develop only ductal lesions that include pancreatic intraepithelial neoplasia (PanINs) and invasive pancreatic ductal adenocarcinomas (PDACs) with sporadic metastasis to the liver
• 11% of mutants exhibit exclusively poorly differentiated adenocarcinomas that can metastasize to the liver, diaphragm, and lung
• 46% of mutants have both ductal lesions and poorly differentiated carcinomas, with a few mutants having moderately differentiated lesions that have an acinar-like appearance
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• 43% of mutants develop only ductal lesions that include pancreatic intraepithelial neoplasia (PanINs) and invasive pancreatic ductal adenocarcinoma (PDACs) with sporadic metastasis to the liver
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:197052 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Ctnnb1tm4Wbm/Ctnnb1tm4Wbm Tg(Pdx1-cre)6Tuv/? pancreata display extensive loss of exocrine tissue
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• shortened lifespan, with a median survival of 29 days, although some mice do survive more than 6 months
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• small body size at birth that persists into adulthood
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• in 17% of mutants that survived beyond 3 months, the pancreas has a liver-like histology
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• numerous tubular structures suggesting pancreas acinar to duct metaplasia, however islets are intact
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• acinar hypoplasia is seen by E16.5 and by 2 months of age, there is a near complete absence of acinar cell structures
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• pancreas weighs on average 30% less than wild-type
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• increase in parenchymal fibrosis
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• decrease in the proliferation rate of pancreatic exocrine progenitors
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• variable degree of surrounding inflammatory infiltrate which becomes more severe by 1 month of age; inflammatory infiltrate is reminiscent of pancreatitis
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• variable degree of surrounding inflammatory infiltrate which becomes more severe by 1 month of age; inflammatory infiltrate is reminiscent of pancreatitis
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• numerous tubular structures suggesting pancreas acinar to duct metaplasia, however islets are intact
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• acinar hypoplasia is seen by E16.5 and by 2 months of age, there is a near complete absence of acinar cell structures
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E9.5, Ipfl (Pdx1)+ cells are found throughout the liver bud unlike in control mice
• at E10.0, the biliary primordium is absent unlike in control mice
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• at E16.5
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• at E9.5, Ipfl (Pdx1)+ cells are found throughout the liver bud unlike in control mice
• at E10.0, the biliary primordium is absent unlike in control mice
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• at E16.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• embryos show varying degrees of shortening of the cystic duct
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• embryos exhibit biliary atresia-like phenotypes such as epithelial deciduation and bile duct stenosis/atresia
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• epithelial deciduation in the gallbladder
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• embryos show varying degrees of shortening of the gallbladder
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• hepatitis in fetuses with normal or mild gallbladder abnormalities but not hepatitis in fetuses with complete lack of the gallbladder
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• embryos show varying degrees of shortening of the cystic duct
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• embryos exhibit biliary atresia-like phenotypes such as epithelial deciduation and bile duct stenosis/atresia
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• epithelial deciduation in the gallbladder
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• embryos show varying degrees of shortening of the gallbladder
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• hepatitis in fetuses with normal or mild gallbladder abnormalities but not hepatitis in fetuses with complete lack of the gallbladder
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• 4/55 embryos exhibit severe gross hepatic lesions
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• bile duct stenosis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice are viable and pancreata show no histologic changes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• median survival 25.5 weeks
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• starting between 6 and 24 weeks with metastasis
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• adenocarcinomas in 9 of 9 invasive carcinomas in the pancreas
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• adenocarcinomas in 9 of 9 invasive carcinomas in the pancreas
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• starting between 6 and 24 weeks
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• increased girth starting between 6 and 24 weeks
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• starting between 6 and 24 weeks with metastasis
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• adenocarcinomas in 9 of 9 invasive carcinomas in the pancreas
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop pancreatic ductal adenocarcinoma (PDAC)
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• mice develop pancreatic ductal adenocarcinoma (PDAC)
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• GFP+ PDAC cells form tumors form more metastases than GFP- PDAC cells when transplanted into recipient mice
• the highly metastatic PDAC subpopulation is enriched for hypoxia-induced genes
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:245611 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 9 of 12 mice develop pancreatic tumors; all cancers are invasive pancreatic ductal adenocarcinoma
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• median lifespan is approximately 120 days with all mice dying around 260 days, which is extended survival compared to conditional mice expressing the Krastm4Tyj allele
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• 9 of 12 mice develop pancreatic tumors; all cancers are invasive pancreatic ductal adenocarcinoma
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:276349 | ||
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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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• mice succumb to invasive pancreatic neoplasms
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• rapid progression, multi-focal and invasive
• pancreatic ductal adenocarcinoma or invasive cystic neoplasms with metastasis to the liver and lungs
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• rapid progression, multi-focal and invasive
• pancreatic ductal adenocarcinoma or invasive cystic neoplasms with metastasis to the liver and lungs
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• median survival 15.5 weeks
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• starting between 6 and 24 weeks with metastasis
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• adenocarcinomas in 21 of 22 invasive carcinomas in the pancreas
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• adenocarcinomas in 21 of 22 invasive carcinomas in the pancreas
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• starting between 6 and 24 weeks
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• increased girth starting between 6 and 24 weeks
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• starting between 6 and 24 weeks with metastasis
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• adenocarcinomas in 21 of 22 invasive carcinomas in the pancreas
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• extended survival compared to control mice with normal Brf1
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• at a reduced rate and with extended survival compared to control mice with normal Brf1
• however, tumors that do form lack recombined Brf1
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• at a reduced rate and with extended survival compared to control mice with normal Brf1
• however, tumors that do form lack recombined Brf1
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 24 of 30 mutants develop pancreatic ductal adenocarcinomas
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• average survival time is 168 days, with a range of 60-254 days
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• 24 of 30 mutants develop pancreatic ductal adenocarcinomas
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in 2 mice
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• all but one mouse, develop large, firm, fibrotic head of the pancreas tumors
• metastatic foci spread to the surface of the liver, lungs, diaphragm, and adrenals with occasional metastasis to the peripancreatic, mesenteric, and retroperitoneal lymph nodes
• mice exhibit the full spectrum of preinvasive lesions
• some tumors are minor, poorly differentiated, or undifferentiated with anaplastic or sarcomatoid features
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• in young mice
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• in one mouse
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• some mice exhibit esophageal papillomas and hyperplasias or papillomatosis of the biliary tree unlike control mice
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• in some mice
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• hemorrhagic
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• in tumor cells
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• in some mice
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• mice frequently exhibit small bowel obstructions unlike control mice
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• in 2 mice
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• all but one mouse, develop large, firm, fibrotic head of the pancreas tumors
• metastatic foci spread to the surface of the liver, lungs, diaphragm, and adrenals with occasional metastasis to the peripancreatic, mesenteric, and retroperitoneal lymph nodes
• mice exhibit the full spectrum of preinvasive lesions
• some tumors are minor, poorly differentiated, or undifferentiated with anaplastic or sarcomatoid features
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• in young mice
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• in 2 mice
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• in 2 mice
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:98936 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• PanIN-1 and PanIN-2, but not PanIN-3 or pancreatic ductal adenocarcinoma, are seen at 22 weeks after birth
(J:214846)
• mice develop intraepithelial neoplasia (PanIN) by 8 weeks of age
(J:276349)
• mice show accelerated PanIN development when treated with cerulein to induce acute pancreatitis
(J:276349)
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• mice develop a varying number of ductal cell proliferation foci in the pancreas from 9 weeks after birth
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• mice develop a varying number of ductal cell proliferation foci in the pancreas from 9 weeks after birth
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• PanIN-1 and PanIN-2, but not PanIN-3 or pancreatic ductal adenocarcinoma, are seen at 22 weeks after birth
(J:214846)
• mice develop intraepithelial neoplasia (PanIN) by 8 weeks of age
(J:276349)
• mice show accelerated PanIN development when treated with cerulein to induce acute pancreatitis
(J:276349)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as in Krastm4Tyj/Kras+ Tg(Ipf1-cre)6Tuv Trp53tm1Thl/Trp53tm1Thlmice succumb to pancreatic tumors with an average latency of 65 days
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice succumb to pancreatic tumors with an average latency of 68 days
|
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 45 days compared with 68 days in Krastm4Tyj/Kras+ Tg(Ipf1-cre)6Tuv Trp53tm1Thl/Trp53tm1Thl
• however, latency is similar to in Brca1tm1Thl/Brca1tm1Thl Krastm4Tyj/Kras+ Tg(Ipf1-cre)6Tuv Trp53tm1Thl/Trp53tm1Thl
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice develop pancreatic tumors; all cancers are invasive pancreatic ductal adenocarcinoma
|
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• median lifespan is approximately 70 days, with all mice dying around 120 days
|
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• all mice develop pancreatic tumors; all cancers are invasive pancreatic ductal adenocarcinoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:276349 | ||
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• survival is similar to mutant mice wild-type for Zdhhc20
|
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• liver metastases are found in 40% of mice compared to 93% of mutant mice wild-type for Zdhhc20
• a similar trend is seen for lung metastases
• both total liver lesion area and number are profoundly reduced
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• due to local or metastatic pancreatic cancer or aggressive oral papillomas
|
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• aggressive oral papillomas
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• within 3 months, mice develop pancreatic intraepithelial neoplasia and microinvasive neoplasms
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• within 3 months
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• in the face and urogenital area at 3 months
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• in the face and urogenital area at 3 months
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• within 3 months, mice develop pancreatic intraepithelial neoplasia and microinvasive neoplasms
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|
• within 3 months
|
|
|
• aggressive oral papillomas
|
|
|
• aggressive oral papillomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:186717 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• phenotypes are relative to the control KPC (KrasG12D/+, p53R172H/+, Pdx1-Cre) PDAC (pancreatic adenocarcinoma) model mice
• size of PDAC primary tumors same as control
|
|
• significantly reduced number of detectable PDAC metastases to liver, lung and other tissues
• reduced migration of PDAC cells in vitro
|
| N |
• survival same as control
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• transitions of epithelium from cuboid to columnar as early as 2 weeks
• number and extent of lesions increases with age
• by 7-10 months occasional animals with invasive and metastatic adenocarcinomas
• lesions eventually found in liver diaphragm and lungs
|
|
• transitions of epithelium from cuboid to columnar as early as 2 weeks
• number and extent of lesions increases with age
• by 7-10 months occasional animals with invasive and metastatic adenocarcinomas
• lesions eventually found in liver diaphragm and lungs
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:87973 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• due to local or metastatic pancreatic cancer or aggressive oral papillomas
|
|
|
• aggressive oral papillomas
|
|
|
• within 3 months, mice develop pancreatic intraepithelial neoplasia and microinvasive neoplasms
|
|
|
• within 3 months
|
|
|
• in the face and urogenital area at 3 months
|
|
|
• in the face and urogenital area at 3 months
|
|
|
• within 3 months, mice develop pancreatic intraepithelial neoplasia and microinvasive neoplasms
|
|
|
• within 3 months
|
|
|
• aggressive oral papillomas
|
|
|
• aggressive oral papillomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:186717 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice succumb to pancreatic tumors with an average latency of 68 days
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die within the first week after birth
|
|
• at P1
|
|
• severe
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E10.5, the biliary primordium is reduced compared to in control mice
|
|
• at E10.5, the biliary primordium is reduced compared to in control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 12 of 40 mutants develop pancreatic ductal adenocarcinomas
|
|
• reduction in pancreatic ductal adenocarcinoma-free survival
|
|
• 12 of 40 mutants develop pancreatic ductal adenocarcinomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 26 of 30 mutants develop pancreatic ductal adenocarcinomas
|
|
• average survival time is 143 days, with a range of 91-191 days
|
|
• 26 of 30 mutants develop pancreatic ductal adenocarcinomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• phenotypes are relative to the control KPC (KrasG12D/+, p53R172H/+, Pdx1-Cre) PDAC (pancreatic adenocarcinoma) model mice
• size of PDAC primary tumors same as control
|
|
• significantly reduced number of detectable PDAC metastases to liver, lung and other tissues
• reduced migration of PDAC cells in vitro
|
|
• survival reduced compared to control
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• mice fed standard chow or a high fat diet exhibit normal insulin tolerance
|
|
|
• in a hyperglycemic clamp study, mice fed standard chow exhibit a higher glucose infusion rate compared with wild-type mice
• mice exhibit reduced STZ-induced hyperglycemic effect compared with wild-type mice
|
|
|
• in mice fed standard chow during the hyperglycemic clamp studies
• in STZ-treated mice
|
|
|
• slightly in fasting mice fed standard chow
• in mice fed a high fat diet
|
|
|
• in mice fed standard chow or a high fat diet
|
|
|
• in mice fed standard chow
• in STZ-treated mice
|
|
|
• mice exhibit are protected from STZ-induced weight loss compared with wild-type mice
|
|
|
• in mice fed standard chow
|
|
|
• beta cells contain increased insulin granules
• however, beta cell size is normal
|
|
|
• in mice fed standard chow
|
|
|
• in mice fed standard chow
• in STZ-treated mice
|
|
|
• mice are protected from STZ-induced beta cell loss via apoptosis compared with wild-type mice
|
|
|
• in mice fed standard chow
|
|
|
• in mice fed standard chow during the hyperglycemic clamp studies
• in STZ-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants develop pancreatic tumors with a similar tumor latency as in mutants with wild-type Cdkn2a, however mice show an increase in the occurrence of more aggressive primary pancreatic ductal adenocarcinomas (PDACs) that quickly metastasized to the liver
|
|
• mutants show an increase in the occurrence of more aggressive primary pancreatic ductal adenocarcinomas
• 77% of mice show invasive PDAC and 85% show poorly differentiated adenocarcinoma
|
|
• 67% incidence of metastases to the liver, 18% incidence to the lung, and 15% incidence to the thymus
• primary pancreatic ductal adenocarcinomas quickly metastasize to the liver
|
|
• mutants develop pancreatic tumors with a similar tumor latency as in mutants with wild-type Cdkn2a, however mice show an increase in the occurrence of more aggressive primary pancreatic ductal adenocarcinomas (PDACs) that quickly metastasized to the liver
|
|
• mutants show an increase in the occurrence of more aggressive primary pancreatic ductal adenocarcinomas
• 77% of mice show invasive PDAC and 85% show poorly differentiated adenocarcinoma
|
|
• due to pancreatic tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival is shorter than either single conditional mutant; mice can survive up to 32 weeks but most have to be euthanized at 24-26 weeks of age
|
|
• all mice develop pancreatic neoplasms between 16 and 24 weeks
• 100% of mice exhibit large cystic pancreata which are mucinous cystadenomas, characterized by the presence of unilocular megacystic lesions with mucoid/watery cyst content, and nodules or peripheral calcification on the cyst wall resembling human mucinous cystic neoplasm
• mucinous cystic neoplasms become malignant pancreatic cancer with nuclear anaplastic features, and show stomach, duodenal or intestinal invasion or liver or lung metastasis, consistent with aggressive pancreatic cystic adenocarcinoma
• 6 week old mice treated with the Wnt inhibitor IWP-2 for 12 weeks show a reduction of or absence of hypertrophic pancreas with cysts
|
|
• tumors exhibit a high incidence of metastasis and invasion
|
|
• 100% of mice exhibit large cystic pancreata which are mucinous cystadenomas
|
|
• all mice develop pancreatic neoplasms between 16 and 24 weeks
• 100% of mice exhibit large cystic pancreata which are mucinous cystadenomas, characterized by the presence of unilocular megacystic lesions with mucoid/watery cyst content, and nodules or peripheral calcification on the cyst wall resembling human mucinous cystic neoplasm
• mucinous cystic neoplasms become malignant pancreatic cancer with nuclear anaplastic features, and show stomach, duodenal or intestinal invasion or liver or lung metastasis, consistent with aggressive pancreatic cystic adenocarcinoma
• 6 week old mice treated with the Wnt inhibitor IWP-2 for 12 weeks show a reduction of or absence of hypertrophic pancreas with cysts
|
|
• cystic fluid of the pancreata shows the induction of the following cytokines: FasL, soluble tumor necrosis factor receptor 1, IL-1beta, IL-6, macrophage inflammatory protein 1gamma, keratinocyte chemoattractant and monocyte chemoattractant protein 1
|
|
• cystic fluid of the pancreata shows the induction of the following cytokines: FasL, soluble tumor necrosis factor receptor 1, IL-1beta, IL-6, macrophage inflammatory protein 1gamma, keratinocyte chemoattractant and monocyte chemoattractant protein 1
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic mucinous cystadenoma | DOID:7235 | J:234310 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• maturation of the prenatal pancreas is disrupted
|
|
• altered gastrointestinal development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• ventral pancreas and gall bladder development is normal at E10.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• in vitro, islets isolated from male mice exhibit an impaired secretory response to glucose (16.7 mM) and KCl (30 mM) in a perifusion assay; the area under the curve (AUC) of the responses to glucose and KCl is reduced
• when KATP channels are held open with diazoxide (100 uM), isolated islets show a blunted secretory response to KCl (30 mM) at 16.7 mM glucose
• impaired insulin secretion is likely due to impaired glucose-dependent amplification of exocytosis
• however, the insulin content of mutant islets is unchanged
|
|
|
• male mice show a significant reduction in the plasma insulin response to oral glucose relative to control littermates
• however, islet morphology and alpha and beta cell mass is normal at 14 weeks of age
|
|
|
• male mice are glucose intolerant following an oral glucose challenge at 6 and 12 weeks of age
• however, insulin tolerance is similar to that in control littermates
|
|
|
• pancreatic beta cells exhibit loss of the glucose-dependent amplification of insulin exocytosis and fail to respond to NADPH and glutathione (GSH), unlike control beta cells
• impaired glucose-dependent amplification of exocytosis can be rescued by reintroduction of the SENP1 catalytic domain (cSENP1) via the patch pipette
• action potential firing is only modestly altered in beta cells, although islet intracellular Ca2+ responses remain largely normal
|
|
|
• in vitro, islets isolated from male mice exhibit an impaired secretory response to glucose (16.7 mM) and KCl (30 mM) in a perifusion assay; the area under the curve (AUC) of the responses to glucose and KCl is reduced
• when KATP channels are held open with diazoxide (100 uM), isolated islets show a blunted secretory response to KCl (30 mM) at 16.7 mM glucose
• impaired insulin secretion is likely due to impaired glucose-dependent amplification of exocytosis
• however, the insulin content of mutant islets is unchanged
|
|
|
• action potential firing is only modestly affected in pancreatic beta cells, as shown by a small but significant reduction in action potential height with no significant differences in inter-spike membrane potential
• however, islet intracellular Ca2+ responses remain largely normal
|
|
N |
• male mice exhibit normal body weight between 6 and 14 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• male mice show an intermediate phenotype of glucose intolerance following an oral glucose challenge
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal growth and morphology
|
|
|
• fasting hyperglycaemia by age 8 weeks
|
|
|
• insulin deficiency by age 8 weeks
|
|
|
• glucose intolerance by age 8 weeks
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| diabetes mellitus | DOID:9351 | J:332319 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following induction of injection of L-arginine or cerulein
|
|
• following induction of injection of L-arginine or cerulein
|
|
• following induction of injection of L-arginine or cerulein
|
|
• following induction of injection of L-arginine or cerulein
|
| N |
• mice exhibit normal pancreatic development
|
|
• following induction of injection of L-arginine or cerulein
|
|
• with elevated serum amylase, exaggerated acinar cell death, leukocyte infiltration, interstitial edema, worsened acute lung injury, and increased serum TNF and IL6 following induction of injection of L-arginine or cerulean
• however, administration of N-acetyl-L-cysteine or neutralization of extracellular Histone and HMGB1 protects mice
|
|
• with elevated serum amylase, exaggerated acinar cell death, leukocyte infiltration, interstitial edema, worsened acute lung injury, and increased serum TNF and IL6 following induction of injection of L-arginine or cerulean
• however, administration of N-acetyl-L-cysteine or neutralization of extracellular Histone and HMGB1 protects mice
|
|
• following induction of injection of L-arginine or cerulein
|
|
• following induction of injection of L-arginine or cerulein
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice show normal pancreatic weight, morphology, and histology up to 12 months of age
|
| N |
• mice are born at the expected frequency
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• plasma insulin levels are increased at 2 min and 5 min of glucose challenge, but not at later 15 and 30 min time point
• however, insulin sensitivity and insulin content remain unchanged
|
|
• plasma insulin levels are increased at 2 min and 5 min of glucose challenge, but not at later 15 and 30 min time point
• however, insulin sensitivity and insulin content remain unchanged
|
|
• mice fed a normal diet show augmented glucose tolerance
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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 12/10/2024 MGI 6.24 |
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