Mouse Genome Informatics
cn1
    Cdkn2atm4Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Smad4tm1Rdp/Smad4tm1Rdp
Ptf1atm1.1(cre)Cvw/Ptf1a+

involves: 129 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• average tumor-free survival is 14 weeks

tumorigenesis
• 5 of 13 mice develop intraductal papillary mucinous neoplasms
• tumor fibrosis is increased compared to mice wild-type for Smad4
• 12 of 13 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4


Mouse Genome Informatics
cn2
    Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Smad4tm1Rdp/Smad4tm1Rdp
Ptf1atm1.1(cre)Cvw/Ptf1a+

involves: 129 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• average tumor-free survival is 8.8 weeks

tumorigenesis
• 4 of 4 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4
• tumor fibrosis is increased compared to mice wild-type for Smad4


Mouse Genome Informatics
cn3
    Braftm1Mmcm/Braf+
Cdkn2atm4Rdp/Cdkn2atm4Rdp

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• Cre-treated mice show scattered papillary adenomas with evidence of subpleural nodules harboring cords of atypical cells trapped within regions of mesenchymal proliferation
• 2/4 mice display multiple lung tumors with a bronchioalveolar component


Mouse Genome Informatics
cn4
    Cdkn2atm4Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Smad4tm1Rdp/Smad4tm1Rdp
Tg(Pdx1-cre)89.1Dam/0

involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• average tumor-free survival is 12.6 weeks

tumorigenesis
• 4 of 12 mice develop intraductal papillary mucinous neoplasms
• tumor fibrosis is increased compared to mice wild-type for Smad4
• 4 of 12 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4
• 8 of 12 mice develop gastric cancer


Mouse Genome Informatics
cn5
    Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Smad4tm1Rdp/Smad4tm1Rdp
Tg(Pdx1-cre)89.1Dam/0

involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• average tumor-free survival is 7.4 weeks

tumorigenesis
• 3 of 10 mice develop intraductal papillary mucinous neoplasms
• tumor fibrosis is increased compared to mice wild-type for Smad4
• 9 of 10 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4
• 5 of 10 mice develop gastric cancer


Mouse Genome Informatics
cn6
    Cdkn2atm4Rdp/Cdkn2a+
Smad4tm1Rdp/Smad4tm1Rdp
Tg(Pdx1-cre)89.1Dam/0

involves: 129S/SvEv * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
N
• tumor-free survival is greater than 52 weeks and only 1 of 10 mice developed an intraductal papillary mucinous neoplasm (J:116130)


Mouse Genome Informatics
cn7
    Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Ptf1atm1.1(cre)Cvw/Ptf1a+

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• average tumor-free survival is 8.6 weeks

tumorigenesis
• 6 of 6 mice develop pancreatic ductal adenocarcinoma


Mouse Genome Informatics
cn8
    Cdkn2atm4Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Ptf1atm1.1(cre)Cvw/Ptf1a+

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• average tumor-free survival is 38 weeks

tumorigenesis
• 6 of 10 mice develop pancreatic ductal adenocarcinoma


Mouse Genome Informatics
cn9
    Cdkn2atm4Rdp/Cdkn2atm4Rdp
Myf6tm1(cre)Mrc/Myf6+
Pax3tm1Mrc/Pax3tm1Mrc

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 4 in 14 mice develop an rhabdomyosarcoma by day 56 to 89

Mouse Models of Human Disease
OMIM IDRef(s)
Rhabdomyosarcoma 2; RMS2 268220 J:93444


Mouse Genome Informatics
cn10
    Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mice develop multiple, aggressive adenocarcinomas in the lungs bilaterally following intranasal delivery of an adenovirus expressing Cre recombinase
• tumor growth is reduced more following two 7.3 Gy fractions of radiation therapy than a single 11.6 Gy fraction
• tumors have decreased BrdU uptake 4 hours after radiation treatment compared to unirradiated tumors, indicating the presence of an intact G1 cell-cycle checkpoint

Mouse Models of Human Disease
OMIM IDRef(s)
Lung Cancer 211980 J:195492


Mouse Genome Informatics
cn11
    Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+

involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mice injected intramuscularly with an adenovirus expressing Cre recombinase into the extremities or into the uterus develop soft tissue sarcomas


Mouse Genome Informatics
cn12
    Cdkn2atm4Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Tg(Pdx1-cre)89.1Dam/0

involves: 129S4/SvJae * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• average tumor-free survival is 38 weeks

tumorigenesis
• 6 of 10 mice develop pancreatic ductal adenocarcinoma


Mouse Genome Informatics
cn13
    Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Tg(Pdx1-cre)89.1Dam/0

involves: 129S4/SvJae * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• invasive ductal adenocarcinomas with extensive regional and distant metastases

Mouse Models of Human Disease
OMIM IDRef(s)
Pancreatic Cancer 260350 J:187012


Mouse Genome Informatics
cn14
    Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Tg(Pdx1-cre)89.1Dam/0

involves: 129S4/SvJae * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• complete penetrance of death due to invasive and metastic cancer by 11 weeks of age (J:87196)
• average tumor-free survival is 8.6 weeks (J:116130)

tumorigenesis
• neoplasms frequently invade the lymphatic and vascular system, indicating metastatic invasion (J:87196)
• 11% of tumors exhibit metastasis (J:108298)
• neoplasms rapidly progressed to become invasive and metastatic tumors
• solid pancreatic tumors, frequently adhering to adjacent organs and the retroperitoneum (J:87196)
• tumors are highly invasive, frequently involving the duodenum, stomach, liver and/or spleen and occasionally obstructing the common bile duct (J:87196)
• 26% of tumors exhibit anaplastic carcinoma histology (J:108298)
• 26% of tumors exhibit sarcomatoid differentiation (J:108298)
• tumors exhibit pathologic features of human pancreatic ductal adenocarcinomas (J:87196)
• 48% of tumors exhibit well differentiated ductal adenocarcinoma histology (J:108298)
• 6 of 6 mice develop pancreatic ductal adenocarcinoma (J:116130)
• earlier onset (3-4 weeks of age) of local premalignant ductal lesions (pancreatic intraepithelial neoplasia) than in mice just expressing the oncogenic form KRAS2 and not deficient for Cdkn2a expression
• pancreatic ductal lesions progress rapidly to invasive pancreatic adenocarcinoma

Mouse Models of Human Disease
OMIM IDRef(s)
Pancreatic Cancer 260350 J:87196 , J:108298


Mouse Genome Informatics
cn15
    Cdkn2atm4Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Tg(Pdx1-cre)89.1Dam/0

involves: 129S4/SvJae * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 69% of tumors exhibit metastasis
• mutants develop pancreatic tumors with an average latency of 34.2 weeks
• 43% of tumors exhibit sarcomatoid differentiation
• 57% of tumors exhibit well differentiated ductal adenocarcinoma histology


Mouse Genome Informatics
cn16
    Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Krastm4Tyj
Tg(Pdx1-cre)89.1Dam/0

involves: 129S4/SvJae * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands

tumorigenesis
• mice develop invasive pancreatic masses that are firm and homogeneous unlike in wild-type mice

homeostasis/metabolism
• PET scans detected abnormal metabolic activity in the abdomen unlike in wild-type mice


Mouse Genome Informatics
cn17
    Cdkn2atm4Rdp/Cdkn2atm4Rdp
Tg(Pdx1-cre)89.1Dam/0

involves: C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
N
• no neoplastic lesions or tumors were observed in the pancreas (J:87196)