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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID 		Cdkn2atm4Rdp
targeted mutation 4, Ronald DePinho
MGI:2687203
Summary 18 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
 		Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Smad4tm1Rdp/Smad4tm1Rdp
Ptf1atm1.1(cre)Cvw/Ptf1a+ 		involves: 129 * FVB/N MGI:3695428
cn2
 		Cdkn2atm4Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Smad4tm1Rdp/Smad4tm1Rdp
Ptf1atm1.1(cre)Cvw/Ptf1a+ 		involves: 129 * FVB/N MGI:3695424
cn3
 		Braftm1Mmcm/Braf+
Cdkn2atm4Rdp/Cdkn2atm4Rdp 		involves: 129P2/OlaHsd MGI:3712026
cn4
 		Cdkn2atm4Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Ptf1atm1.1(cre)Cvw/Ptf1a+ 		involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ MGI:3695432
cn5
 		Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Ptf1atm1.1(cre)Cvw/Ptf1a+ 		involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ MGI:3695431
cn6
 		Cdkn2atm4Rdp/Cdkn2atm4Rdp
Nf1tm1Par/Nf1tm1Par 		involves: 129S1/Sv * 129X1/SvJ MGI:5792147
cn7
 		Cdkn2atm4Rdp/Cdkn2atm4Rdp
Myf6tm1(cre)Mrc/Myf6+
Pax3tm1Mrc/Pax3tm1Mrc 		involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL MGI:3844659
cn8
 		Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+ 		involves: 129S4/SvJae MGI:5491219
cn9
 		Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+ 		involves: 129S4/SvJae * C57BL/6 MGI:5559056
cn10
 		Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Tg(Pdx1-cre)89.1Dam/0 		involves: 129S4/SvJae * C57BL/6 * CBA MGI:5441554
cn11
 		Cdkn2atm4Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Tg(Pdx1-cre)89.1Dam/0 		involves: 129S4/SvJae * C57BL/6 * CBA MGI:3695430
cn12
 		Cdkn2atm4Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Tg(Pdx1-cre)89.1Dam/0 		involves: 129S4/SvJae * C57BL/6 * CBA * FVB/N MGI:5308806
cn13
 		Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Tg(Pdx1-cre)89.1Dam/0 		involves: 129S4/SvJae * C57BL/6 * CBA * FVB/N MGI:2687217
cn14
 		Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Krastm4Tyj
Tg(Pdx1-cre)89.1Dam/0 		involves: 129S4/SvJae * C57BL/6 * DBA/2 MGI:4355874
cn15
 		Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Smad4tm1Rdp/Smad4tm1Rdp
Tg(Pdx1-cre)89.1Dam/0 		involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * CBA * FVB/N MGI:3695429
cn16
 		Cdkn2atm4Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Smad4tm1Rdp/Smad4tm1Rdp
Tg(Pdx1-cre)89.1Dam/0 		involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * CBA * FVB/N MGI:3695426
cn17
 		Cdkn2atm4Rdp/Cdkn2a+
Smad4tm1Rdp/Smad4tm1Rdp
Tg(Pdx1-cre)89.1Dam/0 		involves: 129S/SvEv * C57BL/6 * CBA * FVB/N MGI:3695427
cn18
 		Cdkn2atm4Rdp/Cdkn2atm4Rdp
Tg(Pdx1-cre)89.1Dam/0 		involves: C57BL/6 * CBA * FVB/N MGI:2687205


Genotype
MGI:3695428
cn1
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Smad4tm1Rdp/Smad4tm1Rdp
Ptf1atm1.1(cre)Cvw/Ptf1a+
Genetic
Background		 involves: 129 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Krastm4Tyj mutation (12 available); any Kras mutation (90 available)
Ptf1atm1.1(cre)Cvw mutation (1 available); any Ptf1a mutation (31 available)
Smad4tm1Rdp mutation (0 available); any Smad4 mutation (48 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
endocrine/exocrine glands
increased pancreatic ductal adenocarcinoma incidence ( J:116130 )
• 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

mortality/aging
decreased tumor-free survival time ( J:116130 )
• average tumor-free survival is 8.8 weeks

neoplasm
increased pancreatic ductal adenocarcinoma incidence ( J:116130 )
• 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




Genotype
MGI:3695424
cn2
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Smad4tm1Rdp/Smad4tm1Rdp
Ptf1atm1.1(cre)Cvw/Ptf1a+
Genetic
Background		 involves: 129 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Krastm4Tyj mutation (12 available); any Kras mutation (90 available)
Ptf1atm1.1(cre)Cvw mutation (1 available); any Ptf1a mutation (31 available)
Smad4tm1Rdp mutation (0 available); any Smad4 mutation (48 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
endocrine/exocrine glands
increased pancreatic ductal adenocarcinoma incidence ( J:116130 )
• 12 of 13 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4

mortality/aging
decreased tumor-free survival time ( J:116130 )
• average tumor-free survival is 14 weeks

neoplasm
increased tumor incidence ( J:116130 )
• 5 of 13 mice develop intraductal papillary mucinous neoplasms
• tumor fibrosis is increased compared to mice wild-type for Smad4
increased pancreatic ductal adenocarcinoma incidence ( J:116130 )
• 12 of 13 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4




Genotype
MGI:3712026
cn3
Allelic
Composition		 Braftm1Mmcm/Braf+
Cdkn2atm4Rdp/Cdkn2atm4Rdp
Genetic
Background		 involves: 129P2/OlaHsd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Braftm1Mmcm mutation (3 available); any Braf mutation (60 available)
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
neoplasm
increased lung tumor incidence ( J:121715 )
• 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

respiratory system
increased lung tumor incidence ( J:121715 )
• 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




Genotype
MGI:3695432
cn4
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Ptf1atm1.1(cre)Cvw/Ptf1a+
Genetic
Background		 involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Krastm4Tyj mutation (12 available); any Kras mutation (90 available)
Ptf1atm1.1(cre)Cvw mutation (1 available); any Ptf1a mutation (31 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
decreased tumor-free survival time ( J:116130 )
• average tumor-free survival is 38 weeks

neoplasm
increased pancreatic ductal adenocarcinoma incidence ( J:116130 )
• 6 of 10 mice develop pancreatic ductal adenocarcinoma

endocrine/exocrine glands
increased pancreatic ductal adenocarcinoma incidence ( J:116130 )
• 6 of 10 mice develop pancreatic ductal adenocarcinoma




Genotype
MGI:3695431
cn5
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Ptf1atm1.1(cre)Cvw/Ptf1a+
Genetic
Background		 involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Krastm4Tyj mutation (12 available); any Kras mutation (90 available)
Ptf1atm1.1(cre)Cvw mutation (1 available); any Ptf1a mutation (31 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
decreased tumor-free survival time ( J:116130 )
• average tumor-free survival is 8.6 weeks

neoplasm
increased pancreatic ductal adenocarcinoma incidence ( J:116130 )
• 6 of 6 mice develop pancreatic ductal adenocarcinoma

endocrine/exocrine glands
increased pancreatic ductal adenocarcinoma incidence ( J:116130 )
• 6 of 6 mice develop pancreatic ductal adenocarcinoma




Genotype
MGI:5792147
cn6
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2atm4Rdp
Nf1tm1Par/Nf1tm1Par
Genetic
Background		 involves: 129S1/Sv * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Nf1tm1Par mutation (4 available); any Nf1 mutation (161 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
neoplasm
increased sarcoma incidence ( J:234760 )
• mice injected intramuscularly with an adenovirus expressing cre recombinase (Ad-Cre) develop soft-tissue sarcomas in the region 3 to 12 months after cre exposure
• intramuscular injections of Ad-cre generates a spectrum of high-grade spindle cell sarcomas, including rhabdomyosarcoma and undifferentiated pleomorphic sarcoma
• tumors from both intramuscular and sciatic nerve Ad-Cre injected mice show significant infiltration of mast cells
• tumors arising from intramuscular Ad-Cre injection show higher proliferation than tumors arising from sciatic nerve Ad-Cre injection
• treatment of tumor cells isolated from intramuscularly Ad-Cre injected mice with the MEK inhibitor PD325901results in decreases colony-forming units and cell proliferation
• treatment of Ad-Cre intramuscularly injected mice with the MEK inhibitor PD325901 delays tumor growth, reduces proliferative index of tumors, and decreases CD31+ microvessel density but does not alter mast cell levels in tumors
increased rhabdomyosarcoma incidence ( J:234760 )
• intramuscularly Ad-Cre injected mice develop rhabdomyosarcoma
increased neurofibrosarcoma incidence ( J:234760 )
• mice injected with Ad-Cre in the sciatic nerve develop malignant peripheral nerve sheath tumors in the region at a mean time of 4.1 months after cre exposure

muscle
increased rhabdomyosarcoma incidence ( J:234760 )
• intramuscularly Ad-Cre injected mice develop rhabdomyosarcoma

nervous system
increased neurofibrosarcoma incidence ( J:234760 )
• mice injected with Ad-Cre in the sciatic nerve develop malignant peripheral nerve sheath tumors in the region at a mean time of 4.1 months after cre exposure

Mouse Models of Human Disease
 DO ID OMIM ID(s) Ref(s)
sarcoma DOID:1115 J:234760




Genotype
MGI:3844659
cn7
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2atm4Rdp
Myf6tm1(cre)Mrc/Myf6+
Pax3tm1Mrc/Pax3tm1Mrc
Genetic
Background		 involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Myf6tm1(cre)Mrc mutation (0 available); any Myf6 mutation (19 available)
Pax3tm1Mrc mutation (1 available); any Pax3 mutation (50 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
neoplasm
increased rhabdomyosarcoma incidence ( J:93444 )
• 4 in 14 mice develop an rhabdomyosarcoma by day 56 to 89

muscle
increased rhabdomyosarcoma incidence ( J:93444 )
• 4 in 14 mice develop an rhabdomyosarcoma by day 56 to 89

Mouse Models of Human Disease
 DO ID OMIM ID(s) Ref(s)
alveolar rhabdomyosarcoma DOID:4051 OMIM:268220
 J:93444




Genotype
MGI:5491219
cn8
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Genetic
Background		 involves: 129S4/SvJae
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Krastm4Tyj mutation (12 available); any Kras mutation (90 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
neoplasm
increased lung adenocarcinoma incidence ( J:195492 )
• 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

respiratory system
increased lung adenocarcinoma incidence ( J:195492 )
• 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
 DO ID OMIM ID(s) Ref(s)
lung cancer DOID:1324 OMIM:211980
OMIM:608935
OMIM:612571
OMIM:612593
OMIM:614210
 J:195492




Genotype
MGI:5559056
cn9
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Genetic
Background		 involves: 129S4/SvJae * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Krastm4Tyj mutation (12 available); any Kras mutation (90 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
neoplasm
increased sarcoma incidence ( J:125101 )
• mice injected intramuscularly with an adenovirus expressing Cre recombinase into the extremities or into the uterus develop soft tissue sarcomas

Mouse Models of Human Disease
 DO ID OMIM ID(s) Ref(s)
sarcoma DOID:1115 J:125101




Genotype
MGI:5441554
cn10
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Tg(Pdx1-cre)89.1Dam/0
Genetic
Background		 involves: 129S4/SvJae * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Krastm4Tyj mutation (12 available); any Kras mutation (90 available)
Tg(Pdx1-cre)89.1Dam mutation (2 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
neoplasm
increased pancreatic ductal adenocarcinoma incidence ( J:187012 )
• invasive ductal adenocarcinomas with extensive regional and distant metastases

endocrine/exocrine glands
increased pancreatic ductal adenocarcinoma incidence ( J:187012 )
• invasive ductal adenocarcinomas with extensive regional and distant metastases

Mouse Models of Human Disease
 DO ID OMIM ID(s) Ref(s)
pancreatic carcinoma DOID:4905 OMIM:260350
 J:187012




Genotype
MGI:3695430
cn11
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Tg(Pdx1-cre)89.1Dam/0
Genetic
Background		 involves: 129S4/SvJae * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Krastm4Tyj mutation (12 available); any Kras mutation (90 available)
Tg(Pdx1-cre)89.1Dam mutation (2 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
decreased tumor-free survival time ( J:116130 )
• average tumor-free survival is 38 weeks

neoplasm
increased pancreatic ductal adenocarcinoma incidence ( J:116130 )
• 6 of 10 mice develop pancreatic ductal adenocarcinoma

endocrine/exocrine glands
increased pancreatic ductal adenocarcinoma incidence ( J:116130 )
• 6 of 10 mice develop pancreatic ductal adenocarcinoma




Genotype
MGI:5308806
cn12
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Tg(Pdx1-cre)89.1Dam/0
Genetic
Background		 involves: 129S4/SvJae * C57BL/6 * CBA * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Krastm4Tyj mutation (12 available); any Kras mutation (90 available)
Tg(Pdx1-cre)89.1Dam mutation (2 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
neoplasm
increased pancreas tumor incidence ( J:108298 )
• mutants develop pancreatic tumors with an average latency of 34.2 weeks
• 43% of tumors exhibit sarcomatoid differentiation
increased pancreatic ductal adenocarcinoma incidence ( J:108298 )
• 57% of tumors exhibit well differentiated ductal adenocarcinoma histology
increased metastatic potential ( J:108298 )
• 69% of tumors exhibit metastasis

endocrine/exocrine glands
increased pancreas tumor incidence ( J:108298 )
• mutants develop pancreatic tumors with an average latency of 34.2 weeks
• 43% of tumors exhibit sarcomatoid differentiation
increased pancreatic ductal adenocarcinoma incidence ( J:108298 )
• 57% of tumors exhibit well differentiated ductal adenocarcinoma histology




Genotype
MGI:2687217
cn13
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Tg(Pdx1-cre)89.1Dam/0
Genetic
Background		 involves: 129S4/SvJae * C57BL/6 * CBA * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Krastm4Tyj mutation (12 available); any Kras mutation (90 available)
Tg(Pdx1-cre)89.1Dam mutation (2 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
decreased tumor-free survival time ( J:87196 , J:116130 )
• 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)

neoplasm
increased pancreas tumor incidence ( J:87196 , J:108298 )
• 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)
increased pancreatic ductal adenocarcinoma incidence ( J:87196 , J:108298 , J:116130 )
• 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)
increased pancreatic intraepithelial neoplasia incidence ( J:87196 )
• 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
increased metastatic potential ( J:87196 , J:108298 )
• neoplasms frequently invade the lymphatic and vascular system, indicating metastatic invasion (J:87196)
• 11% of tumors exhibit metastasis (J:108298)
increased malignant tumor incidence ( J:87196 )
• neoplasms rapidly progressed to become invasive and metastatic tumors

endocrine/exocrine glands
increased pancreas tumor incidence ( J:87196 , J:108298 )
• 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)
increased pancreatic ductal adenocarcinoma incidence ( J:87196 , J:108298 , J:116130 )
• 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)
increased pancreatic intraepithelial neoplasia incidence ( J:87196 )
• 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
 DO ID OMIM ID(s) Ref(s)
pancreatic ductal adenocarcinoma DOID:3498 J:87196 , J:108298




Genotype
MGI:4355874
cn14
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Krastm4Tyj
Tg(Pdx1-cre)89.1Dam/0
Genetic
Background		 involves: 129S4/SvJae * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Krastm4Tyj mutation (12 available); any Kras mutation (90 available)
Tg(Pdx1-cre)89.1Dam mutation (2 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype

Pancreatic tumors in Krastm4Tyj/Krastm4Tyj Trim33tm1Los/Trim33tm1Los Tg(Pdx1-cre)89.1Dam/0 and Krastm4Tyj/Krastm4Tyj Cdkn2atm4Rdp/Cdkn2atm4Rdp Tg(Pdx1-cre)89.1Dam/0 mice

endocrine/exocrine glands
increased pancreas tumor incidence ( J:151781 )
• mice develop invasive pancreatic masses that are firm and homogeneous unlike in wild-type mice

neoplasm
increased pancreas tumor incidence ( J:151781 )
• mice develop invasive pancreatic masses that are firm and homogeneous unlike in wild-type mice

homeostasis/metabolism
abnormal metabolism ( J:151781 )
• PET scans detected abnormal metabolic activity in the abdomen unlike in wild-type mice

growth/size/body
pancreas cyst ( J:151781 )




Genotype
MGI:3695429
cn15
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2atm4Rdp
Krastm4Tyj/Kras+
Smad4tm1Rdp/Smad4tm1Rdp
Tg(Pdx1-cre)89.1Dam/0
Genetic
Background		 involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * CBA * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Krastm4Tyj mutation (12 available); any Kras mutation (90 available)
Smad4tm1Rdp mutation (0 available); any Smad4 mutation (48 available)
Tg(Pdx1-cre)89.1Dam mutation (2 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
decreased tumor-free survival time ( J:116130 )
• average tumor-free survival is 7.4 weeks

neoplasm
increased tumor incidence ( J:116130 )
• 3 of 10 mice develop intraductal papillary mucinous neoplasms
• tumor fibrosis is increased compared to mice wild-type for Smad4
increased stomach tumor incidence ( J:116130 )
• 5 of 10 mice develop gastric cancer
increased pancreatic ductal adenocarcinoma incidence ( J:116130 )
• 9 of 10 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4

digestive/alimentary system
increased stomach tumor incidence ( J:116130 )
• 5 of 10 mice develop gastric cancer

endocrine/exocrine glands
increased pancreatic ductal adenocarcinoma incidence ( J:116130 )
• 9 of 10 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4




Genotype
MGI:3695426
cn16
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Smad4tm1Rdp/Smad4tm1Rdp
Tg(Pdx1-cre)89.1Dam/0
Genetic
Background		 involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * CBA * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Krastm4Tyj mutation (12 available); any Kras mutation (90 available)
Smad4tm1Rdp mutation (0 available); any Smad4 mutation (48 available)
Tg(Pdx1-cre)89.1Dam mutation (2 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
decreased tumor-free survival time ( J:116130 )
• average tumor-free survival is 12.6 weeks

neoplasm
increased tumor incidence ( J:116130 )
• 4 of 12 mice develop intraductal papillary mucinous neoplasms
• tumor fibrosis is increased compared to mice wild-type for Smad4
increased stomach tumor incidence ( J:116130 )
• 8 of 12 mice develop gastric cancer
increased pancreatic ductal adenocarcinoma incidence ( J:116130 )
• 4 of 12 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4

digestive/alimentary system
increased stomach tumor incidence ( J:116130 )
• 8 of 12 mice develop gastric cancer

endocrine/exocrine glands
increased pancreatic ductal adenocarcinoma incidence ( J:116130 )
• 4 of 12 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4




Genotype
MGI:3695427
cn17
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2a+
Smad4tm1Rdp/Smad4tm1Rdp
Tg(Pdx1-cre)89.1Dam/0
Genetic
Background		 involves: 129S/SvEv * C57BL/6 * CBA * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Smad4tm1Rdp mutation (0 available); any Smad4 mutation (48 available)
Tg(Pdx1-cre)89.1Dam mutation (2 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
neoplasm
neoplasm ( J:116130 )
N
• tumor-free survival is greater than 52 weeks and only 1 of 10 mice developed an intraductal papillary mucinous neoplasm




Genotype
MGI:2687205
cn18
Allelic
Composition		 Cdkn2atm4Rdp/Cdkn2atm4Rdp
Tg(Pdx1-cre)89.1Dam/0
Genetic
Background		 involves: C57BL/6 * CBA * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm4Rdp mutation (0 available); any Cdkn2a mutation (66 available)
Tg(Pdx1-cre)89.1Dam mutation (2 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
neoplasm
neoplasm ( J:87196 )
N
• no neoplastic lesions or tumors were observed in the pancreas




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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Send questions and comments to User Support. 		last database update
12/10/2024
MGI 6.24 		The Jackson Laboratory