Phenotypes Associated with This Genotype

Genotype
MGI:5431966

• Allelic Composition: Tg(RIP1-Tag)2Dh/0
• Genetic Background: involves: C57BL/6J * DBA/2J

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

mortality/aging

premature death ( J:50695 )

• mutants die at 9-12 weeks of age; almost complete penetrance

• mutants placed on a high sugar diet to counteract hypoglycemia liver longer

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:50695 )

• hyperplasia of the islets of Langerhans

• organization of alpha and delta cells is disrupted in islets

decreased pancreatic alpha cell number ( J:50695 )

• reduced numbers of alpha cells in islets

increased pancreatic beta cell number ( J:50695 )

• islets are densely packed with beta-cells

decreased pancreatic delta cell number ( J:50695 )

• reduced numbers of delta cells in islets

increased pancreas tumor incidence ( J:50695 )

• mutants placed on a high sugar diet to counteract hypoglycemia develop solid pancreatic tumors between 10 and 20 weeks of age; tumors are pure beta-cell tumors

• no evidence that tumors metastasize other organs

increased insulinoma incidence ( J:205389 )

• mice develop insulinomas, showing differentiated epithelial adenoma and invasive carcinoma

• mice treated with AEW541, a small molecule tyrosine kinase inhibitor, from 7-10 weeks of age, from 10-12 weeks of age, or between 9 and 11 weeks at varying doses do not show a reduction in overall tumor burden or tumor incidence

increased pancreatic islet cell carcinoma incidence ( J:205389 )

• mice show invasive carcinoma

• mice treated with AEW541 from 7-10 weeks (prevention trial) show a reduction of average tumor malignancy, dropping form 50% carcinoma to 30% carcinoma

• mice treated with AEW541 between 9 and 11 weeks at varying doses show a dose dependent decrease of malignancy

• however, mice treated with AEW541 from 10-12 weeks do not show a significant effect on tumor malignancy

neoplasm

increased pancreas tumor incidence ( J:50695 )

• mutants placed on a high sugar diet to counteract hypoglycemia develop solid pancreatic tumors between 10 and 20 weeks of age; tumors are pure beta-cell tumors

• no evidence that tumors metastasize other organs

increased insulinoma incidence ( J:205389 )

• mice develop insulinomas, showing differentiated epithelial adenoma and invasive carcinoma

• mice treated with AEW541, a small molecule tyrosine kinase inhibitor, from 7-10 weeks of age, from 10-12 weeks of age, or between 9 and 11 weeks at varying doses do not show a reduction in overall tumor burden or tumor incidence

increased pancreatic islet cell carcinoma incidence ( J:205389 )

• mice show invasive carcinoma

• mice treated with AEW541 from 7-10 weeks (prevention trial) show a reduction of average tumor malignancy, dropping form 50% carcinoma to 30% carcinoma

• mice treated with AEW541 between 9 and 11 weeks at varying doses show a dose dependent decrease of malignancy

• however, mice treated with AEW541 from 10-12 weeks do not show a significant effect on tumor malignancy

homeostasis/metabolism

hypoglycemia ( J:50695 , J:205389 )

• mice succumb to hypoglycemia due to high insulin levels produced by developing insulinomas (J:205389)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
insulinoma		DOID:3892		J:205389
pancreatic carcinoma		DOID:4905	OMIM:260350	J:50695