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Phenotypes Associated with This Genotype
Genotype
MGI:5431966
Allelic
Composition
Tg(RIP1-Tag)2Dh/0
Genetic
Background
involves: C57BL/6J * DBA/2J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(RIP1-Tag)2Dh mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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
• hyperplasia of the islets of Langerhans
• organization of alpha and delta cells is disrupted in islets
• reduced numbers of alpha cells in islets
• islets are densely packed with beta-cells
• reduced numbers of delta cells in islets
• 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
• 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
• 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
• 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
• 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
• 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
• 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


Contributing Projects:
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
09/08/2020
MGI 6.15
The Jackson Laboratory