Mouse Genome Informatics
cn1
    Itgb1tm1Ref/Itgb1tm1Ref
Tg(Ins2-cre)1Heed/?
Tg(RIP1-Tag)2Dh/?

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J * CBA * DBA/2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• derived cells have fewer projections
• derived cell lines exhibit decreased binding to collagen IV
• more derived tumor cells are arrested in G0/G1 than in Itgb1tm1Ref Tg(RIP1-Tag)2Dh controls
• cultured cells die within a week after plating compared to Itgb1tm1Ref Tg(RIP1-Tag)2Dh derived cells
• more derived tumor cells are arrested in G0/G1 than in Itgb1tm1Ref Tg(RIP1-Tag)2Dh controls

tumorigenesis
• 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
• 60% of mice have an increase in the number of disseminated tumor cell emboli within lymphatic vessels near tumors compared to 7.7% in Itgb1tm1Ref Tg(RIP1-Tag)2Dh mice
• however, no metastasis is detected in mice with tumors
• tumor volume is reduced compared to that in Itgb1tm1Ref Tg(RIP1-Tag)2Dh mice
• tumor cell proliferation is significantly reduced and apoptotic rate is reduced compared to Itgb1tm1Ref Tg(RIP1-Tag)2Dh mice


Mouse Genome Informatics
cn2
    Itgb1tm4Ref/Itgb1tm4Ref
Tg(Ins2-cre)1Heed/?
Tg(RIP1-Tag)2Dh/?

involves: C57BL/6 * C57BL/6J * CBA * DBA/2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• similar to Itgb1tm1Ref Tg(Ins2-cre)1Heed Tg(RIP1-Tag)2Dh, mice exhibit reduced tumor burden and increased tumor cell embolization in the lymphatics


Mouse Genome Informatics
cx3
    Itgb1tm1Ref/Itgb1tm1Ref
Tg(RIP1-Tag)2Dh/?

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 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


Mouse Genome Informatics
cx4
    Fn1tm1Bwg/Fn1tm1Bwg
Tg(RIP1-Tag)2Dh/0

involves: 129S4/SvJae * BALB/c * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• the number of angiogenic islets and tumor progression are not different from Tg(RIP1-Tag)2Dh hemizygotes

cardiovascular system
N
• no difference in tumor angiogenesis is seen (J:93027)


Mouse Genome Informatics
cx5
    Fn1tm1Ksek/Fn1tm1Ksek
Tg(RIP1-Tag)2Dh/0

involves: 129S4/SvJae * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• the number of angiogenic islets and tumor progression are not different from Tg(RIP1-Tag)2Dh hemizygotes

cardiovascular system
N
• no difference in tumor angiogenesis is seen (J:93027)


Mouse Genome Informatics
cx6
    Bcl2l1tm1.1Mam/Bcl2l1tm1.1Mam
Tg(Ins2-cre)25Mgn/0
Tg(RIP1-Tag)2Dh/0

involves: 129S6/SvEvTac * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 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
OMIM IDRef(s)
Pancreatic Cancer 260350 J:146436


Mouse Genome Informatics
cx7
    Bcl2l1tm1.1Mam/Bcl2l1tm1.1Mam
Tg(RIP1-Tag)2Dh/0

involves: 129S6/SvEvTac * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 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
OMIM IDRef(s)
Pancreatic Cancer 260350 J:146436


Mouse Genome Informatics
cx8
    Mfge8tm1Mcu/Mfge8tm1Mcu
Tg(RIP1-Tag)2Dh/?

involves: 129X1/SvJ * C57BL/6J * C57BL/6NCr * DBA/2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• there is a decrease in invasive type 2 tumors compared to in Tg(RIP1-Tag)2Dh transgenic mice
• mice have a 20% reduction in tumor vessel permeability compared to in Tg(RIP1-Tag)2Dh transgenic mice
• 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
• 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
• there is a two-fold increase in apoptosis in microinvasive carcinomas

hematopoietic system
• 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
• 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


Mouse Genome Informatics
cx9
    Plautm1Mlg/Plautm1Mlg
Tg(RIP1-Tag)2Dh/0

involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• at 13.5 weeks (end stage), mice homozygous for Plautm1Mlg 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
N
• at 10.5 weeks of age, mice homozygous for Plautm1Mlg and hemizygous for Tg(RIP1-Tag)2Dh show no differences in the frequency of angiogenic switching among premalignant islets relative to RIP1-Tag2 hemizygotes (J:65019)


Mouse Genome Informatics
tg10
    Tg(RIP1-Tag)2Dh/0
involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• average lifespan is about 12.6 weeks

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


Mouse Genome Informatics
tg11
    Tg(RIP1-Tag)2Dh/0
involves: C57BL/6J * DBA/2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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

tumorigenesis
• 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

homeostasis/metabolism

Mouse Models of Human Disease
OMIM IDRef(s)
Pancreatic Cancer 260350 J:50695


Mouse Genome Informatics
tg12
    Tg(RIP1-Tag)2Dh/?
C3.Cg-Tg(RIP1-Tag)2Dh
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• transgenic mice develop pancreatic beta cell tumors