Mouse Genome Informatics
ht1
    Krastm4Tyj/Kras+
involves: 129S4/SvJae
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• treatment with adenoviral Cre to induce oncogenic Kras expression results in lung tumor development, but causes a lower tumor burden and decreased overall tumor area compared to induced mutants on a Spry2-null background
• mice develop lung adenomas with a few adenocarcinomas following intratracheal administration of an adenovirus expressing Cre (Ad-Cre)
• treatment with MLN4924, a small molecular inhibitor of NAE, beginning at 13 weeks after Ad-Cre administration reduces tumor burden, with a reduction in both number of hyperplastic areas and adenomas and size of the tumors
• a few adenocarcinomas develop in mice following Ad-Cre administration

Mouse Models of Human Disease
OMIM IDRef(s)
Lung Cancer 211980 J:207982


Mouse Genome Informatics
cn2
    Krastm4Tyj/Krastm4Tyj
B6.129S4-Krastm4Tyj
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• primary mouse embryonic fibroblast treated with adenoviral-cre exhibit enhanced growth rate compared with wild-type cells


Mouse Genome Informatics
cn3
    Krastm4Tyj/Kras+
B6.129S4-Krastm4Tyj
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase have a median survival of 79 days

tumorigenesis
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase develop noninvasive adenoma and adenocarcinoma over a 6-10 week period, characterized by epithelial cell proliferation without destruction of alveolar walls or stromal reaction
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase develop noninvasive adenoma and adenocarcinoma over a 6-10 week period, characterized by epithelial cell proliferation without destruction of alveolar walls or stromal reaction


Mouse Genome Informatics
cn4
    Krastm4Tyj/Kras+
either: (involves: 129S4/SvJae) or (involves: 129S4/SvJae * C3H/HeJ)
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• after ovarian intrabursal injection of an adenovirus expressing Cre, mutants develop benign ovarian endometriosis-like lesions, however no invasive ovarian tumors are seen up to 10 months following adenoviral injection

growth/size/body
• 47% of mutants develop peritoneal endometriosis following ovarian intrabursal injection of an adenovirus expressing Cre
• however, mice injected with adenovirus expressing Cre directly into the peritoneum do not develop peritoneal endometriosis

reproductive system
• after ovarian intrabursal injection of an adenovirus expressing Cre, mutants develop benign ovarian endometriosis-like lesions, however no invasive ovarian tumors are seen up to 10 months following adenoviral injection

Mouse Models of Human Disease
OMIM IDRef(s)
Endometriosis, Susceptibility to, 1 131200 J:96296


Mouse Genome Informatics
cn5
    Krastm4Tyj/Kras+
involves: 129S4/SvJae
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• median life span of cre adenovirus-treated mice is 32 weeks

tumorigenesis
• tumors from cre adenovirus-treated mice exhibit increased cell proliferation compared to in tumors from Krastm4Tyj/Kras+ Rbl2tm2Tyj/Rbl2tm2Tyj mice
• cre adenovirus-treated mice develop smaller tumors than in cre adenovirus-treated Krastm4Tyj/Kras+ Rbl2tm2Tyj/Rbl2tm2Tyj mice
• mice treated with adenovirus cre develop lung lesions in 4 to 6 months (J:147590)
• cre adenovirus-treated mice develop lung adenocarcinomas, papillary adenomas and bronchiolar hyperplasia and dysplasia (J:147590)
• cre adenovirus-treated mice develop fewer tumors than in Krastm4Tyj/Kras+ Rb1tm3Tyj/Rb1tm3Tyj mice (J:147590)
• large tumors easily visible on the surface of the lungs at eight weeks after Cre-adenovirus treatment (J:158937)
• presence of atypical adenomatous hyperplasia after Cre-adenovirus treatment
• the most common lesion is adenocarcinoma after Cre-adenovirus treatment
• in cre adenovirus-treated mice

respiratory system
• in cre adenovirus-treated mice
• cre adenovirus-treated mice develop bronchiolar hyperplasia and dysplasia unlike wild-type mice
• in cre adenovirus-treated mice
• presence of epithelial hyperplasia after Cre-adenovirus treatment

immune system
• following injection of a cre adenovirus in the ovarian bursa, mice with endometriosis also exhibit an increase in spleen and regional lymph nodes T regulatory cells compared with un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice

hematopoietic system
• following injection of a cre adenovirus in the ovarian bursa, mice with endometriosis also exhibit an increase in spleen and regional lymph nodes T regulatory cells compared with un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice

reproductive system
• following injection of a cre adenovirus in the ovarian bursa, mice develop ovarian lesions consisting of endometrial glandular epithelium unlike un-injected Krastm4Tyj micefollowing injection of a cre adenovirus in the ovarian bursa, mice develop ovarian lesions consisting of endometrial glandular epithelium unlike un-injected Krastm4Tyj mice


Mouse Genome Informatics
cn6
    Krastm4Tyj/Kras+
involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• lung adenocarcinomas cover 11% of lung area 9 weeks after administration of a Cre-recombinase expressing adenovirus

Mouse Models of Human Disease
OMIM IDRef(s)
Lung Cancer 211980 J:203686


Mouse Genome Informatics
cn7
    Krastm4Tyj/Kras+
Tgfbr2tm1.2Hlm/Tgfbr2tm1.2Hlm

B6.129-Krastm4Tyj Tgfbr2tm1.2Hlm
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase have a median survival of 43 days

tumorigenesis
• tumors of Cre adenoviral treated mutants show transmural invasion of vessels and pleural invasion, and regional metastases to mediastinal lymph nodes
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase develop tumors similar to human mixed subtype adenocarcinomas; they show progression of a pure noninvasive lung adenocarcinoma to an adenocarcinoma with mixed invasive morphology and metastatic potential
• tumors of mutants treated with Cre adenovirus show evidence of inflammatory cell recruitment and tumor microenvironment remodeling with neoangiogenesis not seen in homozygous cre adenovirus treated Krastm4Tyj mice

hematopoietic system
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit and increase in B cells in the lungs compared to homozygous cre adenovirus treated Krastm4Tyj mice
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit and increase in T cells in the lungs compared to homozygous cre adenovirus treated Krastm4Tyj mice
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit a lower myeloid cell population in the lungs than controls

immune system
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit and increase in B cells in the lungs compared to homozygous cre adenovirus treated Krastm4Tyj mice
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit and increase in T cells in the lungs compared to homozygous cre adenovirus treated Krastm4Tyj mice
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit a lower myeloid cell population in the lungs than controls

Mouse Models of Human Disease
OMIM IDRef(s)
Lung Cancer 211980 J:177379


Mouse Genome Informatics
cn8
    Krastm4Tyj/Kras+
Map2k7tm1.1Twad/Map2k7tm1.2Twad

B6.Cg-Krastm4Tyj Map2k7tm1.1Twad/Map2k7tm1.2Twad
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

tumorigenesis
• following adenovirus cre infection, mice exhibit increased lung tumor burden compared with control mice

cellular
• following adenovirus cre infection, mice exhibit impaired DNA damage response compared with control mice

homeostasis/metabolism
• following adenovirus cre infection, mice exhibit impaired DNA damage response compared with control mice


Mouse Genome Informatics
cn9
    Krastm4Tyj/Kras+
Ptf1atm1.1(cre)Cvw/Ptf1a+

B6.Cg-Krastm4Tyj Ptf1atm1.1(cre)Cvw
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• at 34 weeks of age, 4 of 10 mice develop metastasis to the lung and liver compared to 6 of 10 metastasis at 48 weeks in Krastm4Tyj Ptf1atm1.1(cre)Cvw heterozygotes
• pancreatic tumors exhibit higher proliferation rates than in Krastm4Tyj Ptf1atm1.1(cre)Cvw heterozygotes

endocrine/exocrine glands
• pancreatic weight is greater than in Krastm4Tyj Ptf1atm1.1(cre)Cvw heterozygotes


Mouse Genome Informatics
cn10
    Krastm4Tyj/Kras+
Ptf1atm1.1(cre)Cvw/Ptf1a+
Tg(MUC1)79.24Gend/0

B6.Cg-Krastm4Tyj Ptf1atm1.1(cre)Cvw Tg(MUC1)79.24Gend
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• at 48 weeks, 6 of 10 mice develop metastasis to the lung and liver compared to 4 of 10 metastasis at 34 weeks of age in Krastm4Tyj Ptf1atm1.1(cre)Cvw Tg(MUC1)79.24Gend heterozygotes
• pancreatic tumors exhibit lower proliferation rates than in Krastm4Tyj Ptf1atm1.1(cre)Cvw Tg(MUC1)79.24Gend heterozygotes


Mouse Genome Informatics
cn11
    Apctm2Rak/Apctm2Rak
Krastm4Tyj/Kras+

involves: 129 * 129S4/SvJae * C57BL/6J * SJL
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• 64% of tumors that develop in mutant colons injected with an adenovirus expressing cre recombinase are adenomas
• 36% of tumors that develop in mutant colons injected with an adenovirus expressing cre recombinase are carcinomas
• 20% of mutants injected with an adenovirus expressing cre recombinase in the distal colon to inactivate Apc exhibit spontaneous gross liver metastases starting 24 weeks after adenoviral injection; these lesions are adenocarcinomas
• 96% of mutants injected with an adenovirus expressing cre recombinase in the distal colon to inactivate Apc develop distal colonic tumors as little as 3 weeks after viral administration
• rapamycin treatment of mutants with tumors does not result in tumor regression

Mouse Models of Human Disease
OMIM IDRef(s)
Colorectal Cancer; CRC 114500 J:156532


Mouse Genome Informatics
cn12
    Krastm4Tyj/Kras+
Tg(Gfap-cre)77.6Mvs/0

involves: 129 * BALB/c * C57BL/6NHsd
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
N
• mutants do not develop tumors


Mouse Genome Informatics
cn13
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm1Brn
Tg(Pdx1-cre)89.1Dam/0

involves: 129 * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• mutants develop pancreatic tumors with an average latency of 6.2 weeks
• mutants exhibit rapid pancreatic ductal adenocaracinoma progression, developing lethal tumors by 8 weeks of age
• 100% of tumors are well differentiated ductal adenocarcinomas

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


Mouse Genome Informatics
cn14
    Cdkn2atm2.1Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm1Brn
Tg(Pdx1-cre)89.1Dam/0

involves: 129 * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• mutants develop pancreatic tumors with an average latency of 6.5 weeks
• 20% of tumors exhibit anaplastic carcinoma histology
• 80% of tumors exhibit well differentiated ductal adenocarcinoma histology

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


Mouse Genome Informatics
cn15
    Cdkn2atm2.1Rdp/Cdkn2atm2.1Rdp
Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm1Brn
Tg(Pdx1-cre)89.1Dam/0

involves: 129 * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• 20% of tumors exhibit metastasis
• mutants develop pancreatic tumors with an average latency of 7.2 weeks
• 60% of tumors exhibit anaplastic carcinoma histology
• 40% of tumors exhibit well differentiated ductal adenocarcinoma histology

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


Mouse Genome Informatics
cn16
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53+
Tg(Pdx1-cre)89.1Dam/0

involves: 129 * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• 33% of tumors exhibit metastasis
• mutants develop pancreatic tumors with an average latency of 21.8 weeks
• 100% of tumors are well differentiated ductal adenocarcinomas


Mouse Genome Informatics
cn17
    Cdkn2atm2.1Rdp/Cdkn2a+
Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53+
Tg(Pdx1-cre)89.1Dam/0

involves: 129 * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• 25% of tumors exhibit metastasis
• mutants develop pancreatic tumors with an average latency of 14.7 weeks
• 19% of tumors exhibit sarcomatoid differentiation
• 81% of tumors exhibit well differentiated ductal adenocarcinoma histology


Mouse Genome Informatics
cn18
    Cdkn2atm2.1Rdp/Cdkn2atm2.1Rdp
Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53+
Tg(Pdx1-cre)89.1Dam/0

involves: 129 * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• 25% of tumors exhibit metastasis
• mutants develop pancreatic tumors with an average latency of 13.1 weeks
• 25% of tumors exhibit sarcomatoid carcinoma histology
• 75% of tumors exhibit well differentiated ductal adenocarcinoma histology

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


Mouse Genome Informatics
cn19
    Cdkn2atm2.1Rdp/Cdkn2atm2.1Rdp
Krastm4Tyj/Kras+
Tg(Pdx1-cre)89.1Dam/0

involves: 129 * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis