Phenotypes Associated with This Genotype

Genotype
MGI:5898453

• Allelic Composition: Apc^tm2Rak/Apc⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Pdx1-cre)6Tuv/0
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6J * FVB/N * SJL

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:234310 )

• 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

neoplasm

increased pancreas tumor incidence ( J:234310 )

• 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

increased metastatic potential ( J:234310 )

• tumors exhibit a high incidence of metastasis and invasion

increased cystadenoma incidence ( J:234310 )

• 100% of mice exhibit large cystic pancreata which are mucinous cystadenomas

endocrine/exocrine glands

increased pancreas tumor incidence ( J:234310 )

• 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

homeostasis/metabolism

increased circulating cholesterol level ( J:234310 )

increased circulating triglyceride level ( J:234310 )

abnormal cytokine level ( J:234310 )

• 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

immune system

abnormal cytokine level ( J:234310 )

• 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