Phenotypes Associated with This Genotype

Genotype
MGI:5662454

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Ren-cre)#Kwg/0
• Genetic Background: involves: 129 * 129P2/OlaHsd

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

neoplasm

increased glucagonoma incidence ( J:216559 )

• pancreatic tumors and liver metastasis express high levels of glucagon and mice exhibit increased circulating glucagon levels indicating that tumors are glucagonoma

increased pancreatic islet cell carcinoma incidence ( J:216559 )

• mice develop pancreatic neuroendocrine tumors that are classified as metastatic islet cell carcinoma; tumors are nodular and highly vascularized

• marker analysis indicates that both the primary pancreatic tumor and the liver metastases are pancreatic neuroendocrine in origin

increased metastatic potential ( J:216559 )

• metastasis to the liver and lymph node is seen; liver metastases are nodular and highly vascularized

• liver also contains many separate metastatic foci

increased sarcoma incidence ( J:216559 )

• mice develop subcutaneous tumors infrequently at around 3-4 months of age; these tumors have a solid growth pattern and are consistent with high-grade vascular sarcoma

endocrine/exocrine glands

increased glucagonoma incidence ( J:216559 )

• pancreatic tumors and liver metastasis express high levels of glucagon and mice exhibit increased circulating glucagon levels indicating that tumors are glucagonoma

increased pancreatic islet cell carcinoma incidence ( J:216559 )

• mice develop pancreatic neuroendocrine tumors that are classified as metastatic islet cell carcinoma; tumors are nodular and highly vascularized

• marker analysis indicates that both the primary pancreatic tumor and the liver metastases are pancreatic neuroendocrine in origin

mortality/aging

decreased tumor-free survival time ( J:216559 )

• primary mortality is from metastatic pancreatic neuroendocrine disease with lethal onset beginning at around 22 weeks of age

• in rare instances, mice develop subcutaneous tumors and need to be euthanized at around 12-16 weeks of age and in even more rare cases, mice die as early as 8 weeks of age of unknown causes; these cases constitute about 12% of mice

homeostasis/metabolism

increased circulating glucagon level ( J:216559 )

• mice show increased circulating glucagon levels at 4, 5 and 6 months but not at 2 months of age

growth/size/body

decreased body weight ( J:216559 )

• 32% reduction in body weight of sick mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
adenoma		DOID:657		J:216559
pancreatic carcinoma		DOID:4905	OMIM:260350	J:216559