Phenotypes associated with this allele

• Allele Symbol: Tg(RIP1-Tag)2Dh
• Allele Name: transgene insertion 2, Douglas Hanahan
• Allele ID: MGI:2429941
• Summary: 15 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Itgb1^tm1Ref/Itgb1^tm1Ref Tg(Ins2-cre)1Heed/? Tg(RIP1-Tag)2Dh/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J * CBA * DBA/2J	MGI:3715012
cn2	Bcl2l1^tm1.1Mam/Bcl2l1^tm1.1Mam Tg(Ins2-cre)25Mgn/0 Tg(RIP1-Tag)2Dh/0	involves: 129S6/SvEvTac * C57BL/6 * DBA	MGI:3843604
cn3	Itgb1^tm4Ref/Itgb1^tm4Ref Tg(Ins2-cre)1Heed/? Tg(RIP1-Tag)2Dh/?	involves: C57BL/6 * C57BL/6J * CBA * DBA/2J	MGI:3715016
cx4	Itgb1^tm1Ref/Itgb1^tm1Ref Tg(RIP1-Tag)2Dh/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2J	MGI:3715015
cx5	Fn1^tm1Bwg/Fn1^tm1Bwg Tg(RIP1-Tag)2Dh/0	involves: 129S4/SvJae * BALB/c * C57BL/6J	MGI:3056920
cx6	Fn1^tm1Ksek/Fn1^tm1Ksek Tg(RIP1-Tag)2Dh/0	involves: 129S4/SvJae * C57BL/6J	MGI:3056922
cx7	Bcl2l1^tm1.1Mam/Bcl2l1^tm1.1Mam Tg(RIP1-Tag)2Dh/0	involves: 129S6/SvEvTac * C57BL/6 * DBA	MGI:3843606
cx8	Mfge8^tm1Mcu/Mfge8^tm1Mcu Tg(RIP1-Tag)2Dh/?	involves: 129X1/SvJ * C57BL/6J * C57BL/6NCr * DBA/2J	MGI:3718021
cx9	Tg(Ins2-IGF1R)1Dh/0 Tg(RIP1-Tag)2Dh/0	involves: C3H * C57BL/6 * C57BL/6J * DBA/2J	MGI:6256967
cx10	Plau^tm1Mlg/Plau^tm1Mlg Tg(RIP1-Tag)2Dh/0	involves: C57BL/6	MGI:3527475
cx11	Tg(Ins2-Mirc13)E4Biat/0 Tg(RIP1-Tag)2Dh/0	involves: C57BL/6J * C57BL/6N * DBA/2J	MGI:6829611
cx12	Palm^tm1.2Kili/Palm^tm1.2Kili Tg(RIP1-Tag)2Dh/0 Tg(Ins2-VEGFC)#Pepr/0	involves: C57BL/6J * C57BL/6N * DBA/2J	MGI:7621643
tg13	Tg(RIP1-Tag)2Dh/0	involves: C57BL/6	MGI:4821099
tg14	Tg(RIP1-Tag)2Dh/0	involves: C57BL/6J * DBA/2J	MGI:5431966
tg15	Tg(RIP1-Tag)2Dh/?	C3.Cg-Tg(RIP1-Tag)2Dh/Nci	MGI:3757564

Genotype
MGI:3715012

cn1

• Allelic Composition: Itgb1^tm1Ref/Itgb1^tm1Ref; Tg(Ins2-cre)1Heed/?; Tg(RIP1-Tag)2Dh/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J * CBA * DBA/2J

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

cellular

abnormal cell morphology ( J:122649 )

• derived cells have fewer projections

abnormal cell adhesion ( J:122649 )

• derived cell lines exhibit decreased binding to collagen IV

abnormal mitosis ( J:122649 )

• more derived tumor cells are arrested in G0/G1 than in Itgb1^tm1Ref Tg(RIP1-Tag)2Dh controls

abnormal cell death ( J:122649 )

• cultured cells die within a week after plating compared to Itgb1^tm1Ref Tg(RIP1-Tag)2Dh derived cells

early cellular replicative senescence ( J:122649 )

• more derived tumor cells are arrested in G0/G1 than in Itgb1^tm1Ref Tg(RIP1-Tag)2Dh controls

neoplasm

decreased metastatic potential ( J:122649 )

• when derived cell lines are injected into nu/nu mice, metastatic nodules from do not form in the lungs and or liver as they do in wild-type mice

abnormal tumor susceptibility ( J:122649 )

• 60% of mice have an increase in the number of disseminated tumor cell emboli within lymphatic vessels near tumors compared to 7.7% in Itgb1^tm1Ref Tg(RIP1-Tag)2Dh mice

• however, no metastasis is detected in mice with tumors

• tumor volume is reduced compared to that in Itgb1^tm1Ref Tg(RIP1-Tag)2Dh mice

• tumor cell proliferation is significantly reduced and apoptotic rate is reduced compared to Itgb1^tm1Ref Tg(RIP1-Tag)2Dh mice

Genotype
MGI:3843604

cn2

• Allelic Composition: Bcl2l1^tm1.1Mam/Bcl2l1^tm1.1Mam; Tg(Ins2-cre)25Mgn/0; Tg(RIP1-Tag)2Dh/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA

neoplasm

increased pancreas tumor incidence ( J:146436 )

• 13 week old mice have a mean of over 4 tumors with an average volume greater than 50 mm³

• there is a significantly higher proportion of encapsulated, non-invasive tumors in these mice compared to Tg(RIP1-Tag)2Dh transgenics (22.8% vs. 4.3%)

endocrine/exocrine glands

increased pancreas tumor incidence ( J:146436 )

• 13 week old mice have a mean of over 4 tumors with an average volume greater than 50 mm³

• there is a significantly higher proportion of encapsulated, non-invasive tumors in these mice compared to Tg(RIP1-Tag)2Dh transgenics (22.8% vs. 4.3%)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pancreatic carcinoma		DOID:4905	OMIM:260350	J:146436

Genotype
MGI:3715016

cn3

• Allelic Composition: Itgb1^tm4Ref/Itgb1^tm4Ref; Tg(Ins2-cre)1Heed/?; Tg(RIP1-Tag)2Dh/?
• Genetic Background: involves: C57BL/6 * C57BL/6J * CBA * DBA/2J

neoplasm

abnormal tumor susceptibility ( J:122649 )

• similar to Itgb1^tm1Ref Tg(Ins2-cre)1Heed Tg(RIP1-Tag)2Dh, mice exhibit reduced tumor burden and increased tumor cell embolization in the lymphatics

Genotype
MGI:3715015

cx4

• Allelic Composition: Itgb1^tm1Ref/Itgb1^tm1Ref; Tg(RIP1-Tag)2Dh/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2J

neoplasm

abnormal tumor morphology ( J:122649 )

• 7.7% of mice have an increase in the number of disseminated tumor cell emboli within lymphatic vessels near tumors

• however, no metastasis is detected in mice with tumors

Genotype
MGI:3056920

cx5

• Allelic Composition: Fn1^tm1Bwg/Fn1^tm1Bwg; Tg(RIP1-Tag)2Dh/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6J

neoplasm

increased carcinoma incidence ( J:93027 )

• the number of angiogenic islets and tumor progression are not different from Tg(RIP1-Tag)2Dh hemizygotes

cardiovascular system

cardiovascular system phenotype ( J:93027 )

N • no difference in tumor angiogenesis is seen

Genotype
MGI:3056922

cx6

• Allelic Composition: Fn1^tm1Ksek/Fn1^tm1Ksek; Tg(RIP1-Tag)2Dh/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

neoplasm

increased carcinoma incidence ( J:93027 )

• the number of angiogenic islets and tumor progression are not different from Tg(RIP1-Tag)2Dh hemizygotes

cardiovascular system

cardiovascular system phenotype ( J:93027 )

N • no difference in tumor angiogenesis is seen

Genotype
MGI:3843606

cx7

• Allelic Composition: Bcl2l1^tm1.1Mam/Bcl2l1^tm1.1Mam; Tg(RIP1-Tag)2Dh/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA

neoplasm

increased pancreas tumor incidence ( J:146436 )

• 13 week old mice have a mean of 7 tumors with an average volume greater than 40 mm³

• there is a significantly lower proportion of encapsulated, non-invasive tumors in these mice compared to Tg(RIP1-Tag)2Dh transgenics where cre-mediated recombination of Bcl2l1 occurs in pancreatic beta cells

endocrine/exocrine glands

increased pancreas tumor incidence ( J:146436 )

• 13 week old mice have a mean of 7 tumors with an average volume greater than 40 mm³

• there is a significantly lower proportion of encapsulated, non-invasive tumors in these mice compared to Tg(RIP1-Tag)2Dh transgenics where cre-mediated recombination of Bcl2l1 occurs in pancreatic beta cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pancreatic carcinoma		DOID:4905	OMIM:260350	J:146436

Genotype
MGI:3718021

cx8

• Allelic Composition: Mfge8^tm1Mcu/Mfge8^tm1Mcu; Tg(RIP1-Tag)2Dh/?
• Genetic Background: involves: 129X1/SvJ * C57BL/6J * C57BL/6NCr * DBA/2J

neoplasm

decreased metastatic potential ( J:123138 )

• there is a decrease in invasive type 2 tumors compared to in Tg(RIP1-Tag)2Dh transgenic mice

abnormal tumor morphology ( J:123138 )

• mice have a 20% reduction in tumor vessel permeability compared to in Tg(RIP1-Tag)2Dh transgenic mice

decreased tumor growth/size ( J:123138 )

• at 12 and 13.5 weeks of age, tumor burden is decreased 2-fold tumor size and incidence is decreased compared to Tg(RIP1-Tag)2Dh transgenic mice

• tumor size and incidence is decreased compared to Tg(RIP1-Tag)2Dh transgenic mice

increased adenoma incidence ( J:123138 )

• adenoma incidence are increased compared to in Tg(RIP1-Tag)2Dh transgenic mice

• apoptotic cells are less frequent in adenomas compared to in hyperblastic and angiogenic islet cells in the same animals and in Tg(RIP1-Tag)2Dh transgenic mice

increased carcinoma incidence ( J:123138 )

• there is a two-fold increase in apoptosis in microinvasive carcinomas

hematopoietic system

decreased Langerhans cell number ( J:123138 )

• the number of angiogenic islets is decreased by 35% compared to in Tg(RIP1-Tag)2Dh transgenic mice

• proliferation of angiogenic islets is decreased by 25% compared to in Tg(RIP1-Tag)2Dh transgenic mice

• hyperplastic and angiogenic islet apoptosis is increased compared to in Tg(RIP1-Tag)2Dh transgenic mice

immune system

decreased Langerhans cell number ( J:123138 )

• the number of angiogenic islets is decreased by 35% compared to in Tg(RIP1-Tag)2Dh transgenic mice

• proliferation of angiogenic islets is decreased by 25% compared to in Tg(RIP1-Tag)2Dh transgenic mice

• hyperplastic and angiogenic islet apoptosis is increased compared to in Tg(RIP1-Tag)2Dh transgenic mice

Genotype
MGI:6256967

cx9

• Allelic Composition: Tg(Ins2-IGF1R)1Dh/0; Tg(RIP1-Tag)2Dh/0
• Genetic Background: involves: C3H * C57BL/6 * C57BL/6J * DBA/2J

mortality/aging

premature death ( J:205389 )

• mice die around 10 weeks of age

neoplasm

increased insulinoma incidence ( J:205389 )

• mice exhibit accelerated insulinoma progression compared to single Tg(RIP1-Tag)2Dh/0 mice

• mice treated with a small molecule tyrosine kinase inhibitor, AEW541 between 6 and 9 weeks of age results in a moderate, yet not significant, reduction in tumor volume, with no difference in proliferation rate of tumor cells but increased apoptosis rate

increased pancreatic islet cell carcinoma incidence ( J:205389 )

• mice exhibit enhanced tumor malignancy, with an almost complete absence of adenoma and a transition from hyperplastic/angiogenic islets to invasive carcinoma

• treatment with AEW541 fails to repress malignant tumor progression

endocrine/exocrine glands

increased insulinoma incidence ( J:205389 )

• mice exhibit accelerated insulinoma progression compared to single Tg(RIP1-Tag)2Dh/0 mice

• mice treated with a small molecule tyrosine kinase inhibitor, AEW541 between 6 and 9 weeks of age results in a moderate, yet not significant, reduction in tumor volume, with no difference in proliferation rate of tumor cells but increased apoptosis rate

increased pancreatic islet cell carcinoma incidence ( J:205389 )

• mice exhibit enhanced tumor malignancy, with an almost complete absence of adenoma and a transition from hyperplastic/angiogenic islets to invasive carcinoma

• treatment with AEW541 fails to repress malignant tumor progression

Genotype
MGI:3527475

cx10

• Allelic Composition: Plau^tm1Mlg/Plau^tm1Mlg; Tg(RIP1-Tag)2Dh/0
• Genetic Background: involves: C57BL/6

neoplasm

increased carcinoma incidence ( J:65019 )

• at 13.5 weeks (end stage), mice homozygous for Plau^tm1Mlg and hemizygous for Tg(RIP1-Tag)2Dh show no differences in the number of angiogenic islets or collective tumor growth relative to Tg(RIP1-Tag)2Dh hemizygotes

cardiovascular system

cardiovascular system phenotype ( J:65019 )

N • at 10.5 weeks of age, mice homozygous for Plau^tm1Mlg and hemizygous for Tg(RIP1-Tag)2Dh show no differences in the frequency of angiogenic switching among premalignant islets relative to RIP1-Tag2 hemizygotes

Genotype
MGI:6829611

cx11

• Allelic Composition: Tg(Ins2-Mirc13)E4Biat/0; Tg(RIP1-Tag)2Dh/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * DBA/2J

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:314874 )

N • mice exhibit normal glucose serum levels after a 4 h fast unlike mice expressing the Mirc13 transgene alone

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:314874 )

N • mice exhibit normal beta cell mass unlike mice expressing the Mirc13 transgene alone

Genotype
MGI:7621643

cx12

• Allelic Composition: Palm^tm1.2Kili/Palm^tm1.2Kili; Tg(RIP1-Tag)2Dh/0; Tg(Ins2-VEGFC)#Pepr/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * DBA/2J

immune system

abnormal lymphangiogenesis ( J:237034 )

• 12-week-old mice show a significant decrease in the Lyve-1+ lymphatic coverage of pancreatic tumors relative to double transgenic mice that are wild-type for Palm, indicating impaired tumor-associated lymphangiogenesis

• however, no changes in the number of pancreatic tumors, tumor volume, or intratumoral CD31+ blood microvessel density are observed relative to double transgenic mice wild-type for Palm

Genotype
MGI:4821099

tg13

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

mortality/aging

premature death ( J:162648 )

• average lifespan is about 12.6 weeks

neoplasm

increased insulinoma incidence ( J:162648 )

• average tumor volume at 12 weeks of age is about 36 mm cubed

endocrine/exocrine glands

increased insulinoma incidence ( J:162648 )

• average tumor volume at 12 weeks of age is about 36 mm cubed

Genotype
MGI:5431966

tg14

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

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

Genotype
MGI:3757564

tg15

• Allelic Composition: Tg(RIP1-Tag)2Dh/?
• Genetic Background: C3.Cg-Tg(RIP1-Tag)2Dh/Nci

neoplasm

increased insulinoma incidence ( J:80168 )

• transgenic mice develop pancreatic beta cell tumors

endocrine/exocrine glands

increased insulinoma incidence ( J:80168 )

• transgenic mice develop pancreatic beta cell tumors