Mouse Genome Informatics
ht1
    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
• 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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 (J:96296)

growth/size
• 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 (J:96296)

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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 (J:154046)


Mouse Genome Informatics
cn6
    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
• 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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
N
• mutants do not develop tumors (J:154673)


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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 33% of tumors exhibit metastasis
• mutants develop pancreatic tumors with an average latency of 18.3 weeks
• 100% of tumors are sarcomatoid in histology


Mouse Genome Informatics
cn20
    Krastm4Tyj/Kras+
Tg(Scgb1a1-cre)1Kkw/?

involves: 129 * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• early mortality with a median survival of 8 weeks

tumorigenesis
• progressive phenotype characterized by cellular atypia, adenoma, and ultimately adenocarcinoma in CC10 positive cells of bronchial epithelia

immune system
• a robust inflammatory response characterized by an abundant infiltration of alveolar macrophages and neutrophils


Mouse Genome Informatics
cn21
    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
• mice die between 8 and 24 weeks of age
• average tumor-free survival is 15.7 weeks

tumorigenesis
• 12 of 12 mice develop intraductal papillary mucinous neoplasms
• 2 of 12 mice develop pancreatic ductal adenocarcinoma

endocrine/exocrine glands
• seen in all mice


Mouse Genome Informatics
cn22
    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
cn23
    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
cn24
    Krastm4Tyj/Kras+
Mapk8tm1Wag/Mapk8+
Mapk9tm1Mka/Mapk9tm1Mka

involves: 129/Sv * 129P2/OlaHsd * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• following adenovirus cre infection, mice exhibit increased lung tumor burden compared with control mice


Mouse Genome Informatics
cn25
    Krastm4Tyj/Kras+
Pax7tm2.1(cre/ERT2)Fan/Pax7+
Trp53tm1Brn/Trp53tm1Brn

involves: 129/Sv * 129P2/OlaHsd * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• when mice older than 6 weeks are given systemic tamoxifen treatment by intraperitoneal delivery, mice develop multiple tumors (avg. 3.9 per mouse) with 100% penetrance within 1-2 months; median tumor-free survival is 44 days
• tumors develop at various locations, including clinically relevant sites including the orbit
• tamoxifen treated mice develop tumors displaying a histological spectrum ranging from undifferentiated pleomorphic sarcoma (UPS) to rhabdomyosarcoma (RMS)
• tumors mimic embryonic RMS, pleomorphic RMS, or myogenic or nonmyogenic UPS
• sarcomas can appear in the body wall (37%), the extremities (31%), head and neck (23%), with some being subcutaneous (9%)


Mouse Genome Informatics
cn26
    Pggt1btm1Mbrg/Pggt1btm1Mbrg
Krastm4Tyj/Kras+

involves: 129/Sv * 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• cre-activation leads to a rounded cell shape
• however, farnesylation of RHOA and CDC42 restores normal cell shape
• cre-activation leads to decreased cell proliferation
• however, farnesylation of RHOA and CDC42 restores proliferation induced by Krastm4Tyj


Mouse Genome Informatics
cn27
    Krastm4Tyj/Kras+
Pggt1btm1Mbrg/Pggt1btm1Mbrg
Lyz2tm1(cre)Ifo/Lyz2+

involves: 129/Sv * 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice survive longer than Pggt1btm1Mbrg Lyzstm1(cre)Ifo Krastm4Tyj heterozygotes with some surviving until day 98 when they were euthanized

tumorigenesis
• few, very mild adenomatous hyperplasia are present at day 11 and increase in occurence by day 62
• however, many segments of the lung are normal at day 62
• at day 98, progressed and scattered adenomas are present

respiratory system
• lung weight is less than in Pggt1btm1Mbrg Lyzstm1(cre)Ifo Krastm4Tyj heterozygotes but higher than in normal mice

growth/size
• after day 40, mice grow slower than controls
• however, up to day 40 mice grow normally


Mouse Genome Informatics
cn28
    Krastm4Tyj/Kras+
Pggt1btm1Mbrg/Pggt1b+
Lyz2tm1(cre)Ifo/Lyz2+

involves: 129/Sv * 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice are normal until day 17 when they begin to die or must be euthanized median survival is to day 20

tumorigenesis
• tumors range from atypical adenomatous hyperplasia, adenoma and adenocarcinoma at day 11 to diffuse adenocarsinoma that obliterate alveolar space by day 20
• beginning at day 11 and obliterating alveolar space by day 20

respiratory system
• lung weight increases 10-fold between day 18 and 22
• after day 17

immune system
• percentage of neutrophil is higher in peripheral blood than in controls
• percentage of lymphocytes is lower than in controls
• pools of immature myeloid are present in the spleen

hematopoietic system
• pools of immature myeloid are present in the spleen
• myeloid proliferation is increased
• percentage of neutrophil is higher in peripheral blood than in controls
• percentage of lymphocytes is lower than in controls
• pools of immature myeloid are present in the spleen

liver/biliary system
• myeloid infiltration of the liver occurs

growth/size
• after day 17


Mouse Genome Informatics
cn29
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53+
Tg(KRT5-cre/PGR)1Der/?

involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * FVB * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• after RU486 and TPA treatment, 30% of mice develop skin carcinomas compared to 5% of Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes


Mouse Genome Informatics
cn30
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm3Glo
Tg(KRT5-cre/PGR)1Der/?

involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * FVB * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• following treatment with RU486 and TPA, mice develop more tumors than in Krastm4Tyj Trp53tm1Brn/ Trp53tm1Brn Tg(KRT5-cre/PGR)1Der mice
• following treatment with RU486 and TPA, conversion to malignant carcinoma is accelerated relative to in Krastm4Tyj Trp53tm1Brn/ Trp53tm1Brn Tg(KRT5-cre/PGR)1Der mice
• after RU486 and TPA treatment, 60% of tumors that develop are spindle cell carcinomas

homeostasis/metabolism
• following treatment with RU486 and TPA, mice develop more tumors than in Krastm4Tyj Trp53tm1Brn/ Trp53tm1Brn Tg(KRT5-cre/PGR)1Der mice


Mouse Genome Informatics
cn31
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm1Brn
Tg(KRT5-cre/PGR)1Der/?

involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * FVB * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• following treatment with RU486 and TPA, mice develop less tumors than in Krastm4Tyj Trp53tm1Brn/Trp53tm3Glo Tg(KRT5-cre/PGR)1Der mice
• after RU486 and TPA treatment, carcinomas that develop following treatment with RU486 and TPA are squamous cell carcinomas with abundant keratin pearls and an absence of spindle cells

homeostasis/metabolism
• following treatment with RU486 and TPA, mice develop less tumors than in Krastm4Tyj Trp53tm1Brn/Trp53tm3Glo Tg(KRT5-cre/PGR)1Der mice


Mouse Genome Informatics
cn32
    Krastm4Tyj/Kras+
Tg(SFTPC-rtTA)5Jaw/0
Tg(tetO-cre)1Jaw/0

involves: 129/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• death in the early postnatal period

respiratory system
• with doxycycline treatment beginning at E6.5, a dramatic lung branching defect is observed
• at E16.5, lungs show even more severe defects than in Kras:Meox2-cre embryos, with large epithelial-lined pouches in place of finely branched network of airways seen in wild-type
• branching defect persists through late gestation leading to early postnatal lethality
• branching defect originates in epithelium rather than mesenchyme
• markers of ciliated and Clara cells in the bronchi are significantly reduced at E18.5 compared to controls, indicating block in differentiation of lung epithelium


Mouse Genome Informatics
cn33
    Krastm4Tyj/Kras+
Tg(KRT5-cre/PGR)1Der/?

involves: 129/Sv * C57BL/6 * FVB * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 7 to 10 weeks after treatment with RU486 to activate the cre transgene, mice develop epidermal papillomas

integument
• 7 to 10 weeks after treatment with RU486 to activate the cre transgene, mice develop epidermal papillomas


Mouse Genome Informatics
cn34
    Krastm4Tyj/Kras+
Trp53tm3Glo/Trp53+
Tg(KRT5-cre/PGR)1Der/?

involves: 129/Sv * C57BL/6 * FVB * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• after RU486 and TPA treatment, mice develop three-fold more tumors than Krastm4Tyj Trp53tm1Brn heterozygotes and Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
• after RU486 and TPA treatment, 60% of mice develop metastasis in the lungs and/or lymph nodes compared to no wild-type mice
• after RU486 and TPA treatment, 42% of tumors exhibit aneuplody compared to 23% of Krastm4Tyj Trp53tm1Brn heterozygotes and 20% of Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
• after RU486 and TPA treatment, tumors exhibit centrosome amplification in 3% to 5% of tumors cells
• after RU486 and TPA treatment, carcinoma development is accelerated compared to in Krastm4Tyj Trp53tm1Brn heterozygotes and Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
• after RU486 and TPA treatment, 90% of mice develop skin carcinomas compared to 30% of Krastm4Tyj Trp53tm1Brn heterozygotes and 5% of Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes

homeostasis/metabolism
• after RU486 and TPA treatment, mice develop three-fold more tumors than Krastm4Tyj Trp53tm1Brn heterozygotes and Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes


Mouse Genome Informatics
cn35
    Brca2tm1Brn/Brca2tm1Cam
Krastm4Tyj/Kras+
Trp53tm3Tyj/Trp53+
Tg(Pdx1-cre)6Tuv/0

involves: 129P2/OlaHsd * 129S/SvEv * 129S4/SvJae * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• about 18% of assessable tumor cases develop an acinar-cell carcinoma component of pancreatic tumors
• high penetrance (29 of 30 mutants) of pancreatic ductal adenocarcinomas

mortality/aging
• average survival time is 84 days, with a range of 48-110 days

Mouse Models of Human Disease
OMIM IDRef(s)
Pancreatic Cancer 260350 J:166678


Mouse Genome Informatics
cn36
    Brca2tm1Cam/Brca2tm1Brn
Krastm4Tyj/Kras+
Tg(Pdx1-cre)6Tuv/0

involves: 129P2/OlaHsd * 129S/SvEv * 129S4/SvJae * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
• pancreatic insufficiency; spectrum of anomalies are seen from isolated paucity of the islets of Langerhans to complete fibro-inflammatory or cystic degeneration of both the endocrine and exocrine pancreas

endocrine/exocrine glands
• pancreatic insufficiency; spectrum of anomalies are seen from isolated paucity of the islets of Langerhans to complete fibro-inflammatory or cystic degeneration of both the endocrine and exocrine pancreas
• pancreata from 6 day old mutants exhibits an increase in apoptotic cells compared to controls

mortality/aging
• mutants exhibit shortened pancreatic ductal adenocarcinoma-free survival

tumorigenesis
• mutants not succumbing to pancreatic insufficiency later develop pancreatic ductal adenocarcinomas with a moderate latency and incomplete penetrance (6 of 32 mutants)


Mouse Genome Informatics
cn37
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm1Brn
Krt19tm1(cre/ERT)Ggu/Krt19+

involves: 129P2/OlaHsd * 129S2/SvPas * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• tamoxifen treated mice die within 2 months from intestinal cancers before developing skin tumors

tumorigenesis
• when back skin from mutant animals is grafted onto back skin of nude mice, all engrafted mice develop skin tumors, including ulcerative lesions (benign and squamous cell carcinomas) within 2 months of tamoxifen administration
• most tumors that develop are benign
• some tumors that develop are invasive squamous cell carcinomas (SCCs)
• tamoxifen treated mice develop terminal intestinal carcinomas with 2 months of treatment

integument
• when back skin from mutant animals is grafted onto back skin of nude mice, all engrafted mice develop skin tumors, including ulcerative lesions (benign and squamous cell carcinomas) within 2 months of tamoxifen administration
• most tumors that develop are benign
• some tumors that develop are invasive squamous cell carcinomas (SCCs)


Mouse Genome Informatics
cn38
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm1Brn
Shhtm2(cre/ERT2)Cjt/Shh+

involves: 129P2/OlaHsd * 129S2/SvPas * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
N
• no macroscopic or microscopic skin tumors are observed up to 4 months after tamoxifen treatment (J:172048)


Mouse Genome Informatics
cn39
    Krastm4Tyj/Kras+
Map2k7tm1.1Twad/Map2k7tm1.2Twad
Trp53tm1Tyj/Trp53tm1Tyj

involves: 129P2/OlaHsd * 129S2/SvPas * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• following adenovirus cre infection, mice exhibit increased lung tumor burden compared with control mice
• however, tumorigenesis is the same as in Map2k7tm1.1Twad/Map2k7tm1.2Twad Krastm4Tyj/Kras+ mice
• following adenovirus cre infection, mice exhibit more adenocarcinomas than Map2k7tm1.1Twad/Map2k7tm1.2Twad Krastm4Tyj/Kras+ mice


Mouse Genome Informatics
cn40
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53+

involves: 129P2/OlaHsd * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• following cre-adenovirus treatment, all mice develop primary lung tumors
• following cre-adenovirus treatment, lung tumors resemble those found in Krastm4Tyj heterozygotes
• following cre-adenovirus treatment, tumors occupy 24% of lung space
• at 6 weeks following cre-adenovirus treatment, mice have lesions ranging from atypical adenomatous hyperplasia to small adenomas that are smaller than in Krastm4Tyj Trp53tm1Brn homozygotes


Mouse Genome Informatics
cn41
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm2Tyj

involves: 129P2/OlaHsd * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• at 19 weeks following cre-adenovirus treatment, sinonasal adenocarninomas develop in 64% of mice
• following cre-adenovirus treatment, all mice develop primary lung tumors that are similar to those found in Krastm4Tyj Trp53tm1Brn heterozygotes


Mouse Genome Informatics
cn42
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm1Brn

involves: 129P2/OlaHsd * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• following cre-adenovirus treatment, a subset of tumors are highly invasive and grow into the hilus, heart, and overlying pleura
• following cre-adenovirus treatment, lymph node metastases are present in over 50% of mice
• at 19 weeks following cre-adenovirus treatment, sinonasal adenocarninomas develop in 14% of mice
• mice infected with low-titre (5X103) lentiviruses expressing Cre and Nfkbia have either a single lung adenocarcinoma or none at all
• mice infected with high-titre (5X104) lentiviruses expressing Cre and Nfkbia have 6-22 lung adenocarcinomas detected per mouse
• following cre-adenovirus treatment, all mice develop primary lung tumors that are similar to those found in Krastm4Tyj Trp53tm1Brn heterozygotes
• at 6 weeks following cre-adenovirus treatment, mice have lesions ranging from atypical adenomatous hyperplasia to small adenomas that are larger than in Krastm4Tyj Trp53tm1Brn heterozygotes (J:103407)
• lung adenocarcinomas cover 11% of lung area 6 weeks after administration of a Cre-recombinase expressing adenovirus (J:203686)
• following cre-adenovirus treatment, all mice develop advanced pulmonary adenocarinomas (J:103407)
• following cre-adenovirus treatment, multiple tumors are present ranging from well-defined tumors to advanced highly dysplastic lesions containing large sheets of dysplastic cells, abnormal mitoses, and multinucleated giant cells (J:103407)
• seventeen weeks after infection with low-titre (5X103) cre lentiviruses, an average of 30 lung adenocarcinomas are detected per mouse (J:154041)
• seventeen weeks after infection with high-titre (5X104) cre lentiviruses, 90-131 lung adenocarcinomas are detected per mouse (J:154041)
• mice develop multiple, aggressive adenocarcinomas in the lungs bilaterally following intranasal delivery of an adenovirus expressing Cre recombinase (J:195492)
• tumor growth is reduced to a similar extent following either two 7.3 Gy fractions of radiation therapy or a single 11.6 Gy fraction (J:195492)
• tumors incorporate high levels of BrdU 4 hours after radiation treatment similarly to unirradiated tumors, indicating lack of an intact G1 cell-cycle checkpoint (J:195492)

mortality/aging
• mice do not survive to 26 weeks post cre-adenovirus treatment in contrast to Krastm4Tyj Trp53tm1Brn heterozygous mice

Mouse Models of Human Disease
OMIM IDRef(s)
Lung Cancer 211980 J:103407 , J:154041 , J:195492 , J:203686


Mouse Genome Informatics
cn43
    Krastm4Tyj/Kras+
Lyz2tm1(cre)Ifo/Lyz2+

involves: 129P2/OlaHsd * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• the maximum survival is 24 days

respiratory system
• lung weight is 10-fold higher than that in control mice at 3 weeks old

tumorigenesis


Mouse Genome Informatics
cn44
    Krastm4Tyj/Kras+
Raf1tm2Bacc/Raf1tm2Bacc
Ptf1atm1(cre)Hnak/Ptf1a+

involves: 129P2/OlaHsd * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• as in Krastm4Tyj Ptf1atm1(cre)Hnak double heterozygotes


Mouse Genome Informatics
cn45
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm2Tyj
Ptf1atm1(cre)Hnak/Ptf1a+

involves: 129P2/OlaHsd * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• however, treatment with a potent and selective oral pan class I PI3K inhibitor (GDC 0941) blocks tumor growth


Mouse Genome Informatics
cn46
    Krastm4Tyj/Kras+
Rnf7Gt(XE423)Byg/Rnf7tm1.1Ysun

involves: 129P2/OlaHsd * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median survival time of Ad-Cre treated mice is 37.9 weeks, with most mice dying by 60 weeks

tumorigenesis
• mice show reduced lung tumor burden following intratracheal administration of an adenovirus expressing Cre (Ad-Cre) compared to single Kras homozygotes, however the number of hyperplastic loci is not affected
• hyperplasia or adenomas from Ad-Cre treated mice show reduced proliferation compared to single Kras homozygotes


Mouse Genome Informatics
cn47
    Krastm4Tyj/Kras+
Rnf7Gt(XE423)Byg/Rnf7+

involves: 129P2/OlaHsd * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median survival time of Ad-Cre treated mice is 27.6 weeks, with all mice dying by 33 weeks

tumorigenesis
• mice develop lung adenomas with a few adenocarcinomas following intratracheal administration of an adenovirus expressing Cre (Ad-Cre)
• a few adenocarcinomas develop in mice following Ad-Cre administration


Mouse Genome Informatics
cn48
    Fntbtm1.1Mbrg/Fntbtm1.2Mbrg
Krastm4Tyj/Kras+

involves: 129P2/OlaHsd * 129S4/SvJae * BALB/cJ * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• Cre-adenovirus treatment results in G2M cell-cycle arrest in embryonic fibroblasts


Mouse Genome Informatics
cn49
    Fntbtm1.1Mbrg/Fntbtm1.2Mbrg
Krastm4Tyj/Kras+
Pggt1btm1Mbrg/Pggt1btm1.1Mbrg
Lyz2tm1(cre)Ifo/Lyz2+

involves: 129P2/OlaHsd * 129S4/SvJae * BALB/cJ * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median life span is 170 days
• longer median life span than Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice (170 vs. 22 days)

tumorigenesis
• lung weight and histology are indistinguishable from littermate control mice at 3-week old, compare with lung weight is 10-fold higher in Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice
• lung weight and histology are indistinguishable from littermate control mice at 3-week old
• but eventually develop lung tumors at older age


Mouse Genome Informatics
cn50
    Fntbtm1.1Mbrg/Fntbtm1.2Mbrg
Krastm4Tyj/Kras+
Pggt1btm1Mbrg/Pggt1btm1.1Mbrg

involves: 129P2/OlaHsd * 129S4/SvJae * BALB/cJ * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 76% fewer tumors and 79% smaller lesion area than Krastm4Tyj heterozygous mice after Cre-adenovirus treatment
• the lung surface of Cre-adenovirus treated mice is nearly indistinguishable from that of control mice
• 76% fewer tumors and 79% smaller lesion area than Krastm4Tyj heterozygous mice after Cre-adenovirus treatment
• presence of small adenomas after Cre-adenovirus treatment
• adenocarcinoma in 1 of 11 mice after Cre-adenovirus treatment

respiratory system
• presence of epithelial hyperplasia after Cre-adenovirus treatment


Mouse Genome Informatics
cn51
    Fntbtm1.1Mbrg/Fntbtm1.2Mbrg
Krastm4Tyj/Kras+
Lyz2tm1(cre)Ifo/Lyz2+

involves: 129P2/OlaHsd * 129S4/SvJae * BALB/cJ * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• longer life span than Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice (>100 days in some cases)

respiratory system
• lung weight is less than Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice but higher than in normal mice

tumorigenesis
• lung weight is less than Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice


Mouse Genome Informatics
cn52
    Krastm4Tyj/Kras+
Mapkapk2tm1.1Yaff/Mapkapk2tm1.1Yaff
Trp53tm1Brn/Trp53tm1Brn

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• lung adenocarcinomas cover 11% of lung area 6 weeks after administration of a Cre-recombinase expressing adenovirus
• tumor burden progresses from 11% of lung (6 weeks) to 45% at experimental endpoint (12+ weeks) in the presence of a Cre-recombinase expressing adenovirus
• Mapkap2 expressing tumors (MK2+) represent a higher proportion of tumor burden, however over time the proportion of these tumors decreases and the proportion of Mapkapk2 (MK2-) null tumors increases in the presence of a Cre-recombinase expressing adenovirus
• proportion of total lung tumor burden composed of Mapkapk2 (MK2-) null tumors is reduced from 39% to 11% following cisplatin treatment


Mouse Genome Informatics
cn53
    Krastm4Tyj/Kras+
Myod1tm1.1(cre/ERT,TVA)Gcg/Myod1+
Trp53tm1Brn/Trp53tm1Brn

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• when mice older than 6 weeks are given systemic tamoxifen treatment by intraperitoneal delivery, mice develop multiple tumors at clinically relevant sites with a median tumor free survival of 153 days (longer latency than Pax7CE mutants
• tamoxifen treated mice develop sarcomas that are exclusively undifferentiated pleomorphic sarcomas (UPS), myogenic or nonmyogenic in type
• tumors can appear in the body wall, the extremities, or the head and neck region


Mouse Genome Informatics
cn54
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm1Brn

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• extremity sarcomas in mice injected with Ad-Cre invade adjacent skeletal muscle and uterine sarcomas invade the intestinal wall and pancreas
• 20% of mice with large extremity sarcomas develop metastasis to the lungs
• 90% of mice injected intramuscularly with an adenovirus expressing Cre recombinase (Ad-Cre) into the extremities develop soft tissue sarcomas after a median time of 3 months (J:125101)
• high penetrance of soft tissue sarcomas also develops after injection of Ad-Cre into the uterus (J:125101)
• soft tissue sarcomas present as large solitary masses originating at the site of Ad-Cre injection, and are high-grade spindle cell neoplasms (J:125101)
• sarcomas show myofibroblastic differentiation with intracytoplasmic filaments with densities (J:125101)
• gene expression analysis indicates that Ad-Cre induced sarcomas are undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (J:155389)


Mouse Genome Informatics
cn55
    Krastm4Tyj/Kras+
Lrrc17tm1Nik/Lrrc17+
Srpk2tm1Nik/Srpk2+
Tg(Mx1-cre)1Cgn/0

involves: 129P2/OlaHsd * 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
• in pIpC-treated mice similar to in pIpC-treated Krastm4Tyj Tg(Mx1-cre)1Cgn mice

immune system
• pIpC-treated mice develop myeloproliferative disorder with anemia unlike wild-type mice that is similar to in pIpC-treated Krastm4Tyj Tg(Mx1-cre)1Cgn mice

hematopoietic system
• bone marrow cells from pIpC-treated mice spontaneous form colony forming units-granulocyte and macrophage (CFU-GM) in the absence of cytokines unlike wild-type cells
• in pIpC-treated mice similar to in pIpC-treated Krastm4Tyj Tg(Mx1-cre)1Cgn mice
• pIpC-treated mice develop myeloproliferative disorder with anemia unlike wild-type mice that is similar to in pIpC-treated Krastm4Tyj Tg(Mx1-cre)1Cgn mice


Mouse Genome Informatics
cn56
    Krastm4Tyj/Kras+
Map2k7tm1.1Twad/Map2k7tm1.2Twad
Tg(Trp53)bSrn/0

involves: 129P2/OlaHsd * 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
N
• following adenovirus cre infection, mice exhibit the same tumor burden as in control mice (J:170904)


Mouse Genome Informatics
cn57
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53+
Tg(Alb-cre)21Mgn/0

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mean survival is 52 weeks of age

tumorigenesis
• tumors are highly metastatic, with tumors showing invasion into adjacent organs such as the diaphragm, bowel, pancreas and stomach or distant metastasis to the lymph nodes, spleen, lungs, or peritoneal cavity
• intrahepatic cholangiocarcinoma is associated with biliary hamartomas
• mutants develop intrahepatic cholangiocarcinoma as early as 32 weeks of age
• intrahepatic cholangiocarcinoma recapitulates the histologic and molecular features of multistage progression of human intrahepatic cholangiocarcinoma
• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas
• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy
• different grades of differentiation are seen in the same tumor

cardiovascular system
• hepatic lesions frequently show hemorrhage into the peritoneal cavity and exhibit evidence of tumor necrosis


Mouse Genome Informatics
cn58
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm1Brn
Tg(Alb-cre)21Mgn/0

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mean survival is 19 weeks of age

tumorigenesis
• tumors are highly metastatic, with 75% of mutants having tumors showing invasion into adjacent organs such as the diaphragm, bowel, pancreas and stomach or distant metastasis to the lymph nodes, spleen, lungs, or peritoneal cavity
• intrahepatic cholangiocarcinoma is associated with biliary hamartomas
• mutants develop intrahepatic cholangiocarcinoma as early as 9 weeks of age
• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas
• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy
• different grades of differentiation are seen in the same tumor

cardiovascular system
• hepatic lesions frequently show hemorrhage into the peritoneal cavity and exhibit evidence of tumor necrosis


Mouse Genome Informatics
cn59
    Krastm4Tyj/Kras+
Sftpctm1.1(cre/ERT2)Ptch/Sftpc+
Trp53tm1Brn/Trp53tm1Brn

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• many mice do not survive to 13 weeks after tamoxifen treatment due to high tumor burden
• mice display leaky cre expression without tamoxifen treatment and survive a few months longer than tamoxifen-treated animals

tumorigenesis
• after tamoxifen treatment, mice show a more severe phenotype than animals with wild-type Trp53 (greater tumor size, tumor growth and tumor grade); by 3-4 weeks after tamoxifen treatment, several small adenomas of papillary nature are observed in alveoli
• at 10 weeks after tamoxifen injection, many alveoli have large tumors; tumors exhibit enlarged pleomorphic nuclei, aberrant mitosis; tumor giant cells are present
• mice surviving to 13 weeks after tamoxifen treatment have adenocarcinomas in the alveoli of the lungs
• without tamoxifen treatment, mice develop invasive lung adenocarcinomas localized to the alveoli
• bronchioalveolar duct junctions (BADJs) appear normal ( in mice with or without tamoxifen treatment)

respiratory system
• 8 days after tamoxifen treatment, extensive type II cell proliferation is observed compared to wild-type; however, proliferating bronchioalveolar stem cells (BASCs) are rarely observed (at 8 days, 3, 6, 10 and 13 weeks after tamoxifen treatment)
• tumor cells express type II cell markers and are highly proliferative, even without tamoxifen treatment


Mouse Genome Informatics
cn60
    Krastm4Tyj/Kras+
Tg(Fabp1-cre)1Jig/0

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
• mice develop widespread hyperplasia throughout the colonic epithelium
• colonic epithelium has a larger transit amplifying cell zone than wild-type; cells in the colonic epithelium have a higher mitotic index than in wild-type
• hyperplasia is typified by extreme lengthening of the crypts
• large, prominent goblet cells develop in the colon

endocrine/exocrine glands
• hyperplasia is typified by extreme lengthening of the crypts


Mouse Genome Informatics
cn61
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm1Brn
Tg(KRT14-cre/ERT)20Efu/0

involves: 129P2/OlaHsd * 129S4/SvJae * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• lesions are squamous cell carcinomas (SCCs)characterized by fibroblast-like shaped cells and disruption of basal lamina
• numerous microscopic and small invasive SCCs are observed in the dermis of the back skin in addition to the macroscopic lesions

integument
• within 2 months of tamoxifen treatment, animals develop rapidly growing ulcerative skin lesions in the back skin
• lesions are squamous cell carcinomas (SCCs)characterized by fibroblast-like shaped cells and disruption of basal lamina
• numerous microscopic and small invasive SCCs are observed in the dermis of the back skin in addition to the macroscopic lesions


Mouse Genome Informatics
cn62
    Apctm2.1Cip/Apc+
Krastm4Tyj/Kras+
Tg(Fabp1-cre)1Jig/0

involves: 129P2/OlaHsd * 129S4/SvJae * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• animals have greatly reduced life-span compared to mutants expressing wild-type Kras

tumorigenesis
• adenocarcinomas show uniform high-grade dysplasia, including large, fused glands with serrated borders, pseudostratified epithelium, loss of apical-basal polarity, and high nucleus to cytoplasm ratio
• mice have more tumors than mutants expressing wild-type Kras
• terminally differentiated cells are absent from tumors


Mouse Genome Informatics
cn63
    Cdkn2atm2.1Nesh/Cdkn2atm2.1Nesh
Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm1Brn
Tg(Tyr-cre/ERT2)13Bos/0

involves: 129P2/OlaHsd * 129S4/SvJae * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice treated with tamoxifen neonatally die within 14 weeks of treatment due to aggressive melanomas with spindle-like morphology unlike control mice in which only one mouse develops melanoma over a period of 60 weeks

tumorigenesis
• tumor growth is more aggressive than in Cdkn2atm1Rdp/Cdkn2atm1Rdp Tg(Tyr-HRAS)60Lc mice
• tamoxifen-treated mice develop melanomas with spindle-like morphology
• all mice treated with tamoxifen neonatally die within 14 weeks of treatment due to aggressive melanomas with spindle-like morphology unlike control mice in which only one mouse develops melanoma over a period of 60 weeks
• tumors in tamoxifen-treated mice occur on the flank, ear, and tail
• the number of tumors in tamoxifen-treated mice is greater than in similarly treated Cdkn2atm2.1Nesh/Cdkn2atm2.1Nesh Krastm4Tyj/Kras+ Tg(Tyr-cre/ERT2)13Bos mice or Krastm4Tyj/Kras+ Trp53tm1Brn/Trp53tm1Brn Tg(Tyr-cre/ERT2)13Bos mice
• by 15 weeks, 17 of 27 adult mice treated with tamoxifen develop melanomas at the site of application and depilation
• however, no uveal tumors are observed

pigmentation
• tamoxifen-treated mice exhibit melanocytic proliferation unlike wild-type mice
• tamoxifen-treated mice develop pigmented macules in the paws and tail unlike wild-type mice


Mouse Genome Informatics
cn64
    Cdkn2atm2.1Nesh/Cdkn2a+
Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53+
Tg(Tyr-cre/ERT2)13Bos/0

involves: 129P2/OlaHsd * 129S4/SvJae * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• tamoxifen-treated mice develop melanomas with spindle-like morphology
• 3 of 7 (43%) mice treated with tamoxifen neonatally develop melanomas with spindle-like morphology at a median latency greater than 52 weeks compared with Cdkn2atm2.1Nesh/Cdkn2atm2.1Nesh Krastm4Tyj/Kras+ Trp53tm1Brn/Trp53tm1Brn Tg(Tyr-cre/ERT2)13Bos mice whose median latency is 14 weeks

pigmentation
• tamoxifen-treated mice exhibit melanocytic proliferation unlike wild-type mice
• tamoxifen-treated mice develop pigmented macules in the paws and tail unlike wild-type mice


Mouse Genome Informatics
cn65
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm1Brn
Tg(Tyr-cre/ERT2)13Bos/0

involves: 129P2/OlaHsd * 129S4/SvJae * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• tamoxifen-treated mice develop melanomas with spindle-like morphology
• 5 of 11 mice treated with tamoxifen neonatally develop melanomas with spindle-like morphology at a longer latency (median latency 31 weeks) than in Cdkn2atm2.1Nesh/Cdkn2atm2.1Nesh Krastm4Tyj/Kras+ Trp53tm1Brn/Trp53tm1BrnTg(Tyr-cre/ERT2)13Bos mice (median latency 14 weeks)

pigmentation
• tamoxifen-treated mice exhibit melanocytic proliferation unlike wild-type mice
• tamoxifen-treated mice develop pigmented macules in the paws and tail unlike wild-type mice


Mouse Genome Informatics
cn66
    Cdkn2atm2Brn/Cdkn2atm2Brn
Krastm4Tyj/Kras+
Tg(Pdx1-cre)6Tuv/0

involves: 129P2/OlaHsd * 129S4/SvJae * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• after 5 days in culture, pancreatic explants exhibit irregular branching and disorganization with increased proliferation, pseudostratification, nuclear crowding and elongation resembling precancerous lesions
• however, no cysts develop

cellular
• after 5 days in culture, pancreatic explants exhibit irregular branching with increased proliferation


Mouse Genome Informatics
cn67
    Krastm4Tyj/Kras+
Spry2tm1.1Mrt/Spry2tm1.1Mrt
Meox2tm1(cre)Sor/Meox2+

involves: 129P2/OlaHsd * 129S4/SvJaeSor * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• lungs at E12.5 show increased branching compared to Kras; Meox2-cre, Spry2-wild-type lungs; bronchi number is increased, but is still less than age-matched wild-type


Mouse Genome Informatics
cn68
    Krastm4Tyj/Kras+
Sftpctm1.1(cre/ERT2)Ptch/Sftpc+

involves: 129P2/OlaHsd * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• by 18 weeks after tamoxifen treatment, numerous adenomas develop in alveoli; small numbers of cells with features of malignant transformation are observed in some lung sections
• tumors are usually found in proximity to the airways, bronchioalveolar duct junctions (BADJs), or surface of the lung, but lesions are not found in the BADJs
• tumor cells are highly proliferative
• airways and BADJs retain normal architecture


Mouse Genome Informatics
cn69
    Krastm4Tyj/Kras+
Tgfbr2tm1.2Hlm/Tgfbr2tm1.2Hlm
Ptf1atm1.1(cre)Cvw/Ptf1a+

involves: 129S/Sv * 129X1/SvJ * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• some die suddenly with a median survival of 59 days

growth/size
• begin to demonstrate abdominal distension at around 6-7 weeks of age due to pancreatic tumor

tumorigenesis
• although no distant metastasis is seen at 7-10 weeks of age, the few mutants that survive up to 24-27 weeks, show prominent desmoplasia and liver metastasis, lung metastasis, diaphragmatic and duodenal invasion and peritoneal dissemination
• 100% penetrance of pancreatic tumors
• progressive development of pancreatic ductal adenocarcinoma; tumor uniformly occupies the whole pancreas and is irregularly shaped and results in almost complete loss of normal pancreatic tissue
• carcinoma cells frequently show nuclear atypia and invasion beyond the basement membrane
• stromal expansion starts in the early tumorigenesis stages and tumors do not show sarcomatoid architecture
• 100% penetrance and tumors are always accompanied by a whole panel of pancreatic intraepithelial neoplasia (mPanIN) lesions and acinar-ductal metaplasia lesions
• tumors are always accompanied by a whole panel of pancreatic intraepithelial neoplasia (mPanIN) lesions and acinar-ductal metaplasia lesions

liver/biliary system
• duodenum loop is compressed by the tumor, resulting in duodenal and gallbladder dilatation
• at late-stage tumor burden, exhibit multiple necrotic areas in the distal liver parenchyma
• observed sometimes

homeostasis/metabolism
• at late-stage tumor burden (7-10 weeks of age), 32% exhibit portal vein thrombosis; the main trunk of the portal vein is completely obstructed with thrombus
• frequently display bloody ascites

hematopoietic system
• seen frequently

immune system
• seen frequently

behavior/neurological
• a few mutants exhibit paraplegia, most likely because of circulation failure due to oppression of large vessels by the growing tumor

digestive/alimentary system
• duodenum loop is compressed by the tumor, resulting in duodenal and gallbladder dilatation

endocrine/exocrine glands
• duodenum loop is compressed by the tumor, resulting in duodenal and gallbladder dilatation

cardiovascular system
• at late-stage tumor burden (7-10 weeks of age), 32% exhibit portal vein thrombosis; the main trunk of the portal vein is completely obstructed with thrombus


Mouse Genome Informatics
cn70
    Krastm4Tyj/Kras+
Tgfbr2tm1.2Hlm/Tgfbr2+
Ptf1atm1.1(cre)Cvw/Ptf1a+

involves: 129S/Sv * 129X1/SvJ * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• exhibit reduced survival than controls after 200 days of age, with a median survival of 347 days

tumorigenesis
• tumors frequently show gross metastasis to the liver and lung, direct invasion to the duodenum, and also peritoneal dissemination
• frequency of metastasis or invasion is much higher (about 50%) than in similar mutants with homozygous, instead of heterozygous, loss of Tgfbr2
• pancreatic tumors examined demonstrate a dominant sarcomatoid histology (50% or more) as well as the ductal adenocarcinoma
• at 200 days of age or later, show well-differentiated ductal adenocarcinoma in the pancreas head region
• develop pancreatic intraepithelial neoplasia (mPanIN) lesions predominantly in the pancreas tail region


Mouse Genome Informatics
cn71
    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
• mice die between 8 and 24 weeks of age
• average tumor-free survival is 13.1 weeks

endocrine/exocrine glands
• seen in all mice

tumorigenesis
• 5 of 8 mice develop intraductal papillary mucinous neoplasms
• 5 of 8 mice develop gastric cancer with squamous or adenosquamous histology


Mouse Genome Informatics
cn72
    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
cn73
    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
cn74
    Brca2tm1Cam/Brca2+
Krastm4Tyj/Kras+
Trp53tm3Tyj/Trp53+
Tg(Pdx1-cre)6Tuv/0

involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 26 of 30 mutants develop pancreatic ductal adenocarcinomas

mortality/aging
• average survival time is 143 days, with a range of 91-191 days


Mouse Genome Informatics
cn75
    Brca2tm1Cam/Brca2+
Krastm4Tyj/Kras+
Tg(Pdx1-cre)6Tuv/0

involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 12 of 40 mutants develop pancreatic ductal adenocarcinomas

mortality/aging
• reduction in pancreatic ductal adenocarcinoma-free survival


Mouse Genome Informatics
cn76
    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
tumorigenesis
• pancreatic ductal adenocarcinomas (J:87973)
• transitions of epithelium from cuboid to columnar as early as 2 weeks (J:87973)
• extra pancreatic tumors are rare (J:87973)
• number and extent of lesions increases with age (J:87973)
• by 7-10 months occasional animals with invasive and metastatic adenocarcinomas (J:87973)
• lesions eventually found in liver diaphragm and lungs (J:87973)
• average cancer free survival is greater than 52 weeks and 2 of 9 mice develop pancreatic ductal adenocarcinoma (J:116130)

endocrine/exocrine glands

Mouse Models of Human Disease
OMIM IDRef(s)
Pancreatic Cancer 260350 J:87973


Mouse Genome Informatics
cn77
    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
cn78
    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
cn79
    Krastm4Tyj/Kras+
Scgb1a1tm1.1(cre)Fjd/Scgb1a1+

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 survival is 24 weeks

respiratory system
• mutants develop lung lesions that are first detected at 12 weeks of age in alveoli and bronchioles
• mutants develop epithelial lesions termed atypical papillary bronchiolar proliferation that has papillary proliferations of the bronchiolar epithelium located at the bronchiolar terminal site
• however, no carcinomas are seen by 24 weeks of age

tumorigenesis
• mutants develop lung lesions that are first detected at 12 weeks of age in alveoli and bronchioles
• mutants develop epithelial lesions termed atypical papillary bronchiolar proliferation that has papillary proliferations of the bronchiolar epithelium located at the bronchiolar terminal site
• atypical adenomatous hyperplasia lesions and adenomas


Mouse Genome Informatics
cn80
    Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu
Scgb1a1tm1.1(cre)Fjd/Scgb1a1+

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
• mean survival is 8 weeks

immune system
• increase in inflammation in lesions compared to single Kras mutants, with an increase in neutrophil and endothelial cell infiltration; infiltration of these cells increases with malignant progression

respiratory system
• increase in inflammation in lesions compared to single Kras mutants, with an increase in neutrophil and endothelial cell infiltration; infiltration of these cells increases with malignant progression
• by 2 months of age, mutants exhibit tachypnea

tumorigenesis
• mutants have higher numbers of lesions and more extensive tumors than single Kras mutants
• mutants develop distinct bronchial and alveolar tumors
• mutants develop lung lesions as early as 4 weeks of age including proliferative atypical adenomatous hyperplasia lesions
• mutants develop lung lesions as early as 4 weeks of age that includes atypical papillary bronchiolar proliferation
• mucinous bronchioloalveolar cell carcinoma-like lesions, a subtype of lung adenocarcinoma

growth/size
• by 2 months of age, mutants exhibit weight loss


Mouse Genome Informatics
cn81
    Krastm4Tyj/Kras+
Trp53tm1.1Dgk/Trp53tm1.1Dgk

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
tumorigenesis
• following infection with adenovirus-FLPe/IRES/Cre (Ad-FIC)
• following infection with Ad-FIC

Mouse Models of Human Disease
OMIM IDRef(s)
Lung Cancer 211980 J:187012


Mouse Genome Informatics
cn82
    Bak1tm1Thsn/Bak1tm1Thsn
Baxtm1Sjk/Baxtm2Sjk
Krastm4Tyj/Kras+

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• intranasal instillation of an adenovirus expressing Cre recombinase (Ad-Cre) results in the development of sinonasal adenocarcinomas
• however, mice injected intramuscularly with Ad-Cre into the extremities or uterus do not develop soft tissue sarcomas


Mouse Genome Informatics
cn83
    Gfi1tm5.1(GFI1*)Tmo/Gfi1tm5.1(GFI1*)Tmo
Krastm4Tyj/Kras+
Tg(Mx1-cre)1Cgn/0

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• of all pIpC-treated mice faster than control mice

hematopoietic system
• all pIpC-treated mice die of myeloproliferative disorder accompanied by an expansion of myeloid cells in the bone marrow, an infiltration of myeloid cells in the spleen, and the appearance of blast cells in the blood faster than control mice

immune system
• all pIpC-treated mice die of myeloproliferative disorder accompanied by an expansion of myeloid cells in the bone marrow, an infiltration of myeloid cells in the spleen, and the appearance of blast cells in the blood faster than control mice


Mouse Genome Informatics
cn84
    Gfi1tm5.1(GFI1*)Tmo/Gfi1+
Krastm4Tyj/Kras+
Tg(Mx1-cre)1Cgn/0

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• of all pIpC-treated mice faster than control mice

hematopoietic system
• all pIpC-treated mice die of myeloproliferative disorder accompanied by an expansion of myeloid cells in the bone marrow, an infiltration of myeloid cells in the spleen, and the appearance of blast cells in the blood faster than control mice

immune system
• all pIpC-treated mice die of myeloproliferative disorder accompanied by an expansion of myeloid cells in the bone marrow, an infiltration of myeloid cells in the spleen, and the appearance of blast cells in the blood faster than control mice


Mouse Genome Informatics
cn85
    Gfi1tm6.1(GFI1)Tmo/Gfi1tm6.1(GFI1)Tmo
Krastm4Tyj/Kras+
Tg(Mx1-cre)1Cgn/0

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• of all pIpC-treated mice

hematopoietic system
• all pIpC-treated mice die of myeloproliferative disorder accompanied by an expansion of myeloid cells in the bone marrow, an infiltration of myeloid cells in the spleen, and the appearance of blast cells in the blood faster

immune system
• all pIpC-treated mice die of myeloproliferative disorder accompanied by an expansion of myeloid cells in the bone marrow, an infiltration of myeloid cells in the spleen, and the appearance of blast cells in the blood faster


Mouse Genome Informatics
cn86
    Krastm4Tyj/Kras+
Ptf1atm1.1(cre)Cvw/Ptf1a+

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• develop pancreatic intraepithelial neoplasia (mPanIN) lesions within a large amount of normal pancreas


Mouse Genome Informatics
cn87
    Krastm4Tyj/Kras+
Krt19tm1(cre/ERT)Ggu/Krt19+

involves: 129S2/SvPas * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 2-4 months after tamoxifen treatment, tumors develop in the back skin in 33% of treated mice
• skin tumors are benign papillomas with no sign of malignant transformation seen up to 4 months after treatment with tamoxifen
• 2-4 months after tamoxifen treatment, lip tumors develop in 78% of treated mice

integument
• sebaceous cyst formation is observed as result of bulge stem cell proliferation and abnormal hair follicle (HF) differentiation
• 1 month after tamoxifen treatment, Kras activation results in the enlargement of the majority of sebaceous glands
• 1 month after tamoxifen treatment, Kras activation results in transient increase in hair follicle bulge stem cell (SC) proliferation
• hyperproliferative bulge SCs can still undergo terminal differentiation
• 2-4 months after tamoxifen treatment, tumors develop in the back skin in 33% of treated mice
• skin tumors are benign papillomas with no sign of malignant transformation seen up to 4 months after treatment with tamoxifen

endocrine/exocrine glands
• sebaceous cyst formation is observed as result of bulge stem cell proliferation and abnormal hair follicle (HF) differentiation
• 1 month after tamoxifen treatment, Kras activation results in the enlargement of the majority of sebaceous glands

cellular
• 1 month after tamoxifen treatment, Kras activation results in transient increase in hair follicle bulge stem cell (SC) proliferation


Mouse Genome Informatics
cn88
    Krastm4Tyj/Kras+
Shhtm2(cre/ERT2)Cjt/Shh+

involves: 129S2/SvPas * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
N
• no epidermal defects or tumor formation are observed with tamoxifen treatment at day 28 (during period of up to 4 months after cre induction) when hair follicles are in full anlagen (J:172048)


Mouse Genome Informatics
cn89
    Krastm4Tyj/Krastm4Tyj
Trim33tm1Los/Trim33tm1Los
Tg(Pdx1-cre)89.1Dam/0

involves: 129S2/SvPas * 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
• over time endocrine and exocrine components are replaced with abnormal ductal structures
• as early as 3 weeks, mice develop enlarged and dilated ductal structures resembling budding cysts unlike in wild-type mice
• with age, islets become disorganized
• as early 7 weeks
• as early 7 weeks, mice exhibit multifocal cystic lesions unlike wild-type mice
• all mice develop cysts that at 6 weeks occupy 50% of the pancreatic area unlike in wild-type mice
• cysts are composed of epithelial cells with cuboidal or cylindrical morphologies that form numerous papillary projections into the cysts
• papillary projections contain masses of small monomorphic cells with an endocrine morphology
• as early as 3 weeks, mice develop acute inflammation of the pancreas unlike wild-type mice

tumorigenesis
• mice develop pancreatic intraepithelial neoplasia and tumors reminiscent of human intraductal papillary mucinous neoplasm
• however, mice do not exhibit macroscopic evidence of invasive carcinoma
• as early as 3 weeks, mice develop pancreatic intraepithelial neoplasias

immune system
• as early as 3 weeks, mice develop acute inflammation of the pancreas unlike wild-type mice

digestive/alimentary system
• as early as 3 weeks, mice develop enlarged and dilated ductal structures resembling budding cysts unlike in wild-type mice


Mouse Genome Informatics
cn90
    Krastm4Tyj/Kras+
Tg(Prm-cre)58Og/0

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants die between E9.5 and 11.5

embryogenesis
• at E9.5 vasculature is poorly developed; vasculature has a primitive honeycomb-like network lacking branching vitelline vessels, while large vitelline vessels are absent
• marked defect in inner labyrinth layer is observed at E9.5
• fetal blood vessels underlying inner labyrinth layer are absent
• at E9.5, yolk sacs are pale and roughened
• embryos show developmental arrest

cellular
• at death, embryos exhibit widespread apoptosis

cardiovascular system
• fetal blood vessels underlying inner labyrinth layer are absent
• at E9.5 vasculature is poorly developed; vasculature has a primitive honeycomb-like network lacking branching vitelline vessels, while large vitelline vessels are absent


Mouse Genome Informatics
cn91
    Krastm4Tyj/Kras+
Trp53tm2Tyj/Trp53+

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• following cre-adenovirus treatment, all mice develop primary lung tumors that are similar to those found in Krastm4Tyj Trp53tm1Brn heterozygotes (J:103407)
• following cre-adenovirus treatment, tumors occupy 27% of lung space (J:103407)
• mice treated with intratracheal delivery of cre-expressing adenovirus develop lung cancer (J:191425)
• mice infected with higher doses of cre expressing adenovirus present with clinical signs of lung cancer by 15 weeks of treatment while lower dosed animals show signs of disease around 37 weeks (J:191425)
• a subset of tumors from mice treated with intratracheal delivery of cre-expressing adenovirus show loss of heterozygosity of Trp53 (J:191425)
• treatment of mice treated with intratracheal delivery of cre-expressing adenovirus with an miR-34 expressing lentilvirus almost completely abrogates tumor formation (J:191425)
• treatment of mice that have already formed lung tumors following intratracheal delivery of cre-expressing adenovirus with an miR-34 expressing lentilvirus prevents further progression of tumors (J:191425)
• mice treated with intratracheal delivery of cre-expressing adenovirus show evidence that high-grade adenocarcinomas acquire metastatic characteristics of non-small cell lung cancer
• tumors of mice treated with intratracheal delivery of cre-expressing adenovirus are adenocarcinomas and some evidence that high-grade adenocarcinomas acquire metastatic characteristics

immune system
• mice treated with intratracheal delivery of cre-expressing adenovirus exhibit large lungs filled with tumors and inflammation
• the inflammation that develops in the lungs of mice treated with intratracheal delivery of cre-expressing adenovirus occurs after initial nodules develop

behavior/neurological
• mice treated with intratracheal delivery of cre-expressing adenovirus develop a hunched posture in the most severe cases

growth/size
• mice treated with intratracheal delivery of cre-expressing adenovirus exhibit a decline in weight

respiratory system
• mice treated with intratracheal delivery of cre-expressing adenovirus exhibit large lungs filled with tumors and inflammation
• the inflammation that develops in the lungs of mice treated with intratracheal delivery of cre-expressing adenovirus occurs after initial nodules develop
• mice treated with intratracheal delivery of cre-expressing adenovirus exhibit labored breathing

Mouse Models of Human Disease
OMIM IDRef(s)
Lung Cancer 211980 J:191425


Mouse Genome Informatics
cn92
    Krastm4Tyj/Kras+
Trp53tm3Tyj/Trp53+

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• following cre-adenovirus treatment, all mice develop primary lung tumors that are shifted towards more lower grade tumor types
• following cre-adenovirus treatment, tumors occupy 36% of lung space


Mouse Genome Informatics
cn93
    Krastm4Tyj/Kras+
Gt(ROSA)26Sortm1(cre/ERT2)Tyj/Gt(ROSA)26Sor+

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
• adult mice develop widespread hyperplasia throughout the colonic epithelium
• hyperplasia is typified by lengthening of the crypts in adult mice
• large, prominent goblet cells develop in the colon in adult mice

endocrine/exocrine glands
• hyperplasia is typified by lengthening of the crypts in adult mice


Mouse Genome Informatics
cn94
    Krastm4Tyj/Kras+
Gt(ROSA)26Sortm3(CAG-luc)Tyj/Gt(ROSA)26Sor+

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• following induction of expression using an adenoviral cre, mice develop lung tumors as in Krastm4Tyj


Mouse Genome Informatics
cn95
    Krastm4Tyj/Krastm4Tyj
Bhlha15tm3(cre/ERT2)Skz/Bhlha15+

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 2 months after injection with tamoxifen, mice exhibit focal low grade pancreatic intraepithelial neoplasia (PanIN) originating from acinar cells that progresses to carcinoma in situ in some cases by 4 to 12 months following injection with tamoxifen
• tamoxifen treated mice exhibit lesions that progress from normal acinar parenchyma to acinar-ductal metaplastic structures to PanIN with biphenotypic exocrine differentiation
• tamoxifen treated mice exhibit highly proliferative acinar derived PanIN


Mouse Genome Informatics
cn96
    Krastm4Tyj/Krastm4Tyj
Tg(Ela1-cre/ERT)1Dam/0

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• tamoxifen treated and untreated mice develop pancreatic intraepithelial neoplasia (PanIN) that develops from acinar cells


Mouse Genome Informatics
cn97
    Krastm4Tyj/Kras+
Rb1tm3Tyj/Rb1tm3Tyj

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median life span of cre adenovirus-treated mice is 20 weeks

tumorigenesis
• tumors from cre adenovirus-treated mice exhibit lower cell proliferation rates compared to in tumors from Krastm4Tyj heterozygotes
• mice treated with adenovirus cre develop lung lesions in 4 to 6 months
• cre adenovirus-treated mice develop lung adenocarcinomas, papillary adenomas, and bronchiolar hyperplasia and dysplasia
• at end stage, 25% of cre adenovirus-treated mice develop grade 5 tumors, defined by stromal desmoplasia
• cre adenovirus-treated mice develop more numerous tumors than in cre adenovirus-treated Krastm4Tyj heterozygotes and Krastm4Tyj/Kras+ Rbl2tm2Tyj/Rbl2tm2Tyj mice
• in cre adenovirus-treated mice

respiratory system
• cre adenovirus-treated mice develop bronchiolar hyperplasia and dysplasia unlike wild-type mice


Mouse Genome Informatics
cn98
    Krastm4Tyj/Kras+
Rbl2tm2Tyj/Rbl2tm2Tyj

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median life span of cre adenovirus-treated mice is 25 weeks

tumorigenesis
• tumors from cre adenovirus-treated mice exhibit lower cell proliferation rates compared to in tumors from Krastm4Tyj heterozygotes and Krastm4Tyj/Kras+ Rb1tm3Tyj/Rb1tm3Tyj mice
• cre adenovirus-treated mice develop larger tumors than in cre adenovirus-treated Krastm4Tyj heterozygotes and Krastm4Tyj/Kras+ Rb1tm3Tyj/Rb1tm3Tyj mice
• mice treated with adenovirus cre develop lung lesions in 4 to 6 months
• cre adenovirus-treated mice develop lung adenocarcinomas, papillary adenomas and bronchiolar hyperplasia and dysplasia
• 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


Mouse Genome Informatics
cn99
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm1Brn
Tg(Scgb1a1-rtTA)1Jaw/0

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• infiltrating inflammatory cells recruited to tumors in which NF-kB has been inhibited
• tumorigenesis is initiated by infection with lentiviruses expressing Cre and Nfkbia lentiviruses
• doxycycline (Dox)-mediated induction of Nfkbia expression specifically in the tumor cells starting at 16 weeks after tumor initiation results in a significantly diminished tumour growth rate
• tumorigenesis is initiated by infection with lentiviruses expressing Cre and Nfkbia lentiviruses
• doxycycline (Dox)-mediated induction of Nfkbia expression specifically in the tumor cells leads to a significant impairment of tumour development
• tumorigenesis is initiated by infection with lentiviruses expressing Cre and Nfkbia lentiviruses


Mouse Genome Informatics
cn100
    Krastm4Tyj/Krastm4Tyj
Ptf1atm1(cre)Hnak/Ptf1a+

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis


Mouse Genome Informatics
cn101
    Fastm1Ach/Fastm1Ach
Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• triple mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination are protected from developing ovarian cancer, with only 1 of 11 mice developing cancer compared to 9 of 12 double Kras and Pten mutants


Mouse Genome Informatics
cn102
    Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination develop ovarian cancer eight weeks after injection (J:161953)

Mouse Models of Human Disease
OMIM IDRef(s)
Ovarian Cancer 167000 J:161953


Mouse Genome Informatics
cn103
    Krastm4Tyj/Kras+
Trp53tm4Att/Trp53tm4Att

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• after treatment with adenoviral cre, mice develop a significantly increased lung tumor burden unlike mice having mutations in only one of the two transactivation domains with normal tumor levels


Mouse Genome Informatics
cn104
    Gt(ROSA)26Sortm1(RAC1*)Jkis/Gt(ROSA)26Sor+
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 treated with a cre-expressing adenovirus exhibit increased tumor burden due to increased lung cancer cell proliferation compared with Krastm4Tyj heterozygotes treated with a cre-expressing adenovirus
• in mice treated with a cre-expressing adenovirus


Mouse Genome Informatics
cn105
    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
cn106
    Krastm4Tyj/Kras+
Pdpk1tm1Mlw/Pdpk1tm1Mlw
Tg(Ela1-cre/ERT)1Dam/0

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
N
• mice do not develop pancreatic tumors unlike Krastm4Tyj/Kras+ Tg(Ela1-cre/ERT)1Dam mice (J:197054)


Mouse Genome Informatics
cn107
    Krastm4Tyj/Kras+
Tg(Ela1-cre/ERT)1Dam/0

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis


Mouse Genome Informatics
cn108
    Krastm4Tyj/Kras+
Pdpk1tm1Mlw/Pdpk1tm1Mlw
Ptf1atm1(cre)Hnak/Ptf1a+

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• pancreas of older mice exhibit some areas of fatty degeneration
• however, acinar to ductal metaplasia observed in acini from Krastm4Tyj Ptf1atm1(cre)Hnak double heterozygotes is rescued in an in vitro assay

tumorigenesis
N
• pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma observed in Krastm4Tyj Ptf1atm1(cre)Hnak double heterozygotes is rescued (J:197054)


Mouse Genome Informatics
cn109
    Krastm4Tyj/Kras+
Meox2tm1(cre)Sor/Meox2+

involves: 129S4/SvJae * 129S4/SvJaeSor
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• embryos are recovered at a lower frequency (15% vs expected 25%) at E13.5

embryogenesis
N
• mutants show normal vascularization of the yolk sac and placental labyrinth (J:119477)
• fetal-derived hematopoietic progenitors form larger CFU-E (colony-forming unit-erythroid) and BFU-E (burst-forming unit-erythroid) colonies compared with controls
• red blood cells appear immature compared to wild-type and occasionally highly atypical, consisten with a block in erythroid differentiation

cardiovascular system
• excess cushion tissue often leads to obstructed outflow tract
• at E13.5, embryos frequently show double outlet right ventricle
• atrioventricular valve malformations
• all embryonic hearts have prominent septal defects
• heart defects lead to heart failure and death in embryos by ~E14.5
• embryos appear normal at E12.5, but rapidly develop peripheral hemorrhages by E13.5, consistent with heart failure

hematopoietic system
• fetal-derived hematopoietic progenitors form larger CFU-E (colony-forming unit-erythroid) and BFU-E (burst-forming unit-erythroid) colonies compared with controls
• red blood cells appear immature compared to wild-type and occasionally highly atypical, consisten with a block in erythroid differentiation

respiratory system
• defects in lung branching are apparent by E11.5 compared to controls in vivo and in cultured lungs
• decrease in branching is associated with formation of large, fluid-filled sacs rather than normal terminal branches
• at E12.5, mutant lungs exhibit large dilated bronchi whereas wild-type lungs show secondary and tertiary bronchi
• at E14.5, mutants lungs display dilated bronchi and only a few terminal bronchi
• at E14.5, mutants lungs display only a few terminal bronchioles
• at E12.5, lungs exhibit large dilated bronchi; defect is more pronounced at E14.5
• at E12.5, lungs exhibit large dilated bronchi; defect is more pronounced at E14.5

liver/biliary system
• at E12.5 fetal livers show large areas of apoptosis
• at E12.5, fetal livers appear hypocellular

homeostasis/metabolism
• embryos appear normal at E12.5, but rapidly develop edema by E13.5, consistent with heart failure

integument
• embryos appear normal at E12.5, but rapidly develop pallor by E13.5, consistent with heart failure

cellular
• at E12.5 fetal livers show large areas of apoptosis


Mouse Genome Informatics
cn110
    Gt(ROSA)26Sortm1(Notch1)Dam/Gt(ROSA)26Sor+
Krastm4Tyj/Krastm4Tyj
Tg(Ela1-cre/ERT)1Dam/0

involves: 129S4/SvJae * 129S4/SvJaeSor
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• tamoxifen treated and untreated mice develop widespread pancreatic intraepithelial neoplasia (PanIN) that develops from acinar cells
• PanINs proceed to more severe stages than in Krastm4Tyj/Krastm4Tyj Tg(Ela1-cre/ESR1)1Dam mice
• acinar-ductal metaplasia precedes PanIN


Mouse Genome Informatics
cn111
    Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+
Krastm4Tyj/Kras+
Pms2tm2(cre)Lisk/Pms2tm2(cre)Lisk

involves: 129S4/SvJae * 129S4/SvJaeSor
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• numbers of stained spots in intestines is not increased compared to mice without the Kras allele, but size of stained patches increases suggesting sporadic cre activation of Kras which might have a selective advantage for mutant stem cells resulting in clonal expansion and crypt fission

tumorigenesis
• animals become moribund at 5 weeks of age due to high lung tumor burden

cellular
• numbers of stained spots in intestines is not increased compared to mice without the Kras allele, but size of stained patches increases suggesting sporadic cre activation of Kras which might have a selective advantage for mutant stem cells resulting in clonal expansion and crypt fission


Mouse Genome Informatics
cn112
    Gt(ROSA)26Sortm1(Notch1)Dam/Gt(ROSA)26Sor+
Krastm4Tyj/Krastm4Tyj
Tg(Pdx1-cre/Esr1*)35.10Dam/0

involves: 129S4/SvJae * 129S4/SvJaeSor * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mice treated with tamoxifen staring at E10.5 exhibit pancreatic intraepithelial neoplasia (PanIN) that overtakes nearly all of the organ
• mice not treated with tamoxifen develop focal PanIN that are more numerous than in Krastm4Tyj/Krastm4Tyj Tg(Ipf1-cre/Esr1)35.10Dam mice
• acinar-ductal metaplasia precedes PanIN


Mouse Genome Informatics
cn113
    Cdkn2atm1.1Gsu/Cdkn2atm1.1Gsu
Krastm4Tyj/Kras+
Tg(Pdx1-cre)6Tuv/0

involves: 129S4/SvJae * 129S4/SvJaeSor * C57BL/6J * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median survival 25.5 weeks

tumorigenesis
• adenocarcinomas in 9 of 9 invasive carcinomas in the pancreas
• starting between 6 and 24 weeks with metastasis
• adenocarcinomas in 9 of 9 invasive carcinomas in the pancreas

growth/size
• starting between 6 and 24 weeks
• increased girth starting between 6 and 24 weeks

liver/biliary system
• starting between 6 and 24 weeks

homeostasis/metabolism
• starting between 6 and 24 weeks


Mouse Genome Informatics
cn114
    Krastm4Tyj/Kras+
Pik3r1tm1Lca/Pik3r1tm1Lca
Pik3r2tm1Lca/Pik3r2tm1Lca

involves: 129S4/SvJae * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• following administration of inhaled adenovirus cre, mice develop fewer lung tumors than in Krastm4Tyj/Kras+ Pik3r2tm1Lca/Pik3r2tm1Lca or Krastm4Tyj/Kras+ Pik3r2tm1Lca/Pik3r2tm1Lca Pik3r1tm1Lca/Pik3r1+ mice


Mouse Genome Informatics
cn115
    Krastm4Tyj/Kras+
Pik3r2tm1Lca/Pik3r2tm1Lca

involves: 129S4/SvJae * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• following administration of inhaled adenovirus cre


Mouse Genome Informatics
cn116
    Krastm4Tyj/Kras+
Pik3r1tm1Lca/Pik3r1+
Pik3r2tm1Lca/Pik3r2tm1Lca

involves: 129S4/SvJae * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• following administration of inhaled adenovirus cre


Mouse Genome Informatics
cn117
    Gt(ROSA)26Sortm2(Pik3ca*)Dsa/Gt(ROSA)26Sor+
Krastm4Tyj/Kras+
Pdpk1tm1Mlw/Pdpk1tm1Mlw
Ptf1atm1(cre)Hnak/Ptf1a+

involves: 129S4/SvJae * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
N
• mice do not develop acinar to ductal metaplasia (J:197054)

tumorigenesis
N
• mice do not develop pancreatic intraepithelial neoplasia or pancreatic ductal adenocarcinoma (J:197054)


Mouse Genome Informatics
cn118
    Krastm4Tyj/Kras+
Stk11tm1.2Rdp/Stk11tm1.2Rdp

involves: 129S4/SvJae * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• in the lungs of mice treated with cre-expressing adenovirus

immune system
• in the lungs of mice treated with cre-expressing adenovirus


Mouse Genome Informatics
cn119
    Col1a1tm5(tetO-GFP/RNAi:Cdkn2a)Slowe/Col1a1+
Gt(ROSA)26Sortm1(Luc)Kael/Gt(ROSA)26Sortm1(rtTA*M2)Jae
Krastm4Tyj/Kras+
Tg(Scgb1a1-rtTA)1Jaw/0

involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice treated with a cre-expressing adenovirus and treated with doxycycline exhibit reduced survival compared with control mice

tumorigenesis
• mice treated with a cre-expressing adenovirus and treated with doxycycline exhibit increased tumor incidence (size and number) in the lungs with rare noninvasive lung adenomas compared with control mice
• however, mice treated with a cre-expressing adenovirus and treated with doxycycline exhibit tumor regression after doxycycline removal
• in mice treated with a cre-expressing adenovirus and treated with doxycycline

respiratory system
• rapid shallow breathing in mice treated with a cre-expressing adenovirus and treated with doxycycline

growth/size
• in mice treated with a cre-expressing adenovirus and treated with doxycycline


Mouse Genome Informatics
cn120
    Krastm4Tyj/Kras+
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Krt1-15-cre/PGR)22Cot/0

involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * C57BL/6J * SJL/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mice rapidly develop skin tumors beginning 1 month after induction with topical application of RU486 to the back of the skin with 100% penetrance
• tumors that develop after RU486 induction are well-to-moderately differentiated squamous cell carcinomas with an epidermal lineage or basaloid squamous cell carcinomas of unknown stem cell origin
• a subset of benign or locally invasive tumors form adjacent to the squamous cell carcinoma precursor lesions, which are of hair follicle (trichoepitheliomas, basaloid squamous cell carcinoma) or sebaceous gland origin (sebaceous adenomas) after induction with topical application of RU486
• metastases develop between 8 and 18 weeks after induction with RU486, with 28% of tumor-bearing mice developing lung metastasis and 1 of 18 mice showing lymph node metastasis
• a subset of benign or locally invasive tumors form adjacent to the squamous cell carcinoma precursor lesions, which are of hair follicle (trichoepitheliomas, basaloid squamous cell carcinoma) or sebaceous gland origin (sebaceous adenomas) after induction with topical application of RU486
• a few benign papillomas are seen after induction with topical application of RU486

integument
• mice rapidly develop skin tumors beginning 1 month after induction with topical application of RU486 to the back of the skin with 100% penetrance
• tumors that develop after RU486 induction are well-to-moderately differentiated squamous cell carcinomas with an epidermal lineage or basaloid squamous cell carcinomas of unknown stem cell origin
• a subset of benign or locally invasive tumors form adjacent to the squamous cell carcinoma precursor lesions, which are of hair follicle (trichoepitheliomas, basaloid squamous cell carcinoma) or sebaceous gland origin (sebaceous adenomas) after induction with topical application of RU486


Mouse Genome Informatics
cn121
    Gt(ROSA)26Sortm2(Rnf187)Jhai/Gt(ROSA)26Sor+
Krastm4Tyj/Kras+
Tg(Vil-cre)20Syr/0

involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
• mice exhibit increased cell proliferation in the colonic crypt compared with wild-type mice

cellular
• mice exhibit increased cell proliferation in the colonic crypt compared with wild-type mice


Mouse Genome Informatics
cn122
    Gt(ROSA)26Sortm1(Tva)Dsa/Gt(ROSA)26Sor+
Krastm4Tyj/Kras+
Ptf1atm1(cre)Hnak/Ptf1a+

involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median survival of mice infected with RCASBP(A)-shTP53, which knocks down Trp53 expression, is only 151 days compared to 485 days for controls

tumorigenesis
• mice infected with RCASBP(A)-shTP53, which knocks down Trp53 expression, display a significantly shorter latency of pancreatic ductal adenocarcinoma development
• all infected mice develop invasive pancreatic ductal adenocarcinoma within 10 months


Mouse Genome Informatics
cn123
    Fgfr3tm4Cxd/Fgfr3+
Krastm4Tyj/Kras+
Tg(Upk2-cre)6Xrw/0

involves: 129S4/SvJae * 129S6/SvEvTac * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• by 1 year of age, 44% of mutants develop skin papilloma, with tumors reaching 1 cm in diameter by a median of 220 days

mortality/aging
• shorter survival due to skin papillomas, with a survival time between 100-400 days

tumorigenesis
N
• mice aged to 12 month do not develop urothelial hyperplasia or urothelial carcinoma or lung tumors (J:174242)
• by 1 year of age, 44% of mutants develop skin papilloma, with tumors reaching 1 cm in diameter by a median of 220 days


Mouse Genome Informatics
cn124
    Krastm4Tyj/Kras+
Gt(ROSA)26Sortm1(sb13)Tuv/Gt(ROSA)26Sor+
Tg(Pdx1-cre)6Tuv/0
TgTn(sb-T2/Onc)#Dla/0

involves: 129S4/SvJae * 129S6/SvEvTac * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice succumb to invasive pancreatic neoplasms

tumorigenesis
• rapid progression, multi-focal and invasive
• pancreatic ductal adenocarcinoma or invasive cystic neoplasms with metastasis to the liver and lungs


Mouse Genome Informatics
cn125
    Cdkn2atm2.1Rdp/Cdkn2atm2.1Rdp
Krastm4Tyj/Kras+
Tg(Pdx1-cre)6Tuv/0

involves: 129S4/SvJae * 129S6/SvEvTac * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median survival 15.5 weeks

tumorigenesis
• adenocarcinomas in 21 of 22 invasive carcinomas in the pancreas
• starting between 6 and 24 weeks with metastasis
• adenocarcinomas in 21 of 22 invasive carcinomas in the pancreas

growth/size
• starting between 6 and 24 weeks
• increased girth starting between 6 and 24 weeks

liver/biliary system
• starting between 6 and 24 weeks

homeostasis/metabolism
• starting between 6 and 24 weeks


Mouse Genome Informatics
cn126
    Ctnnb1tm1Mmt/Ctnnb1+
Krastm4Tyj/Kras+
Tg(CYP19A1-cre)1Jri/0

involves: 129S4/SvJae * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants die within 3.5-5.5 months of age

tumorigenesis
• female mutants exhibit precancerous lesions in the ovaries at between 4 and 5 weeks of age (J:186144)
• female mutants develop bilateral granulosa cell tumors by 3 months of age (J:186144)

endocrine/exocrine glands
• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked (J:186144)

reproductive system
• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked (J:186144)

homeostasis/metabolism
• at 6 weeks of age in females (J:186144)
• at 6 weeks of age in females (J:186144)
• at 6 weeks of age in females (J:186144)
• at 6 weeks of age in females (J:186144)

cellular
• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked (J:186144)

Mouse Models of Human Disease
OMIM IDRef(s)
Ovarian Cancer 167000 J:186144


Mouse Genome Informatics
cn127
    Ctnnb1tm1Mmt/Ctnnb1+
Krastm4Tyj/Kras+
Amhr2tm3(cre)Bhr/Amhr2+

involves: 129S4/SvJae * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• female mutants develop granulosa cell tumors by 12-14 weeks of age (J:186144)
• male mutants develop granulosa cell tumors of the testis by 4-5 months of age; tumors do not spread or metastasize (J:186144)

reproductive system
• seminiferous tubule degeneration is seen by 4 weeks of age (J:186144)

endocrine/exocrine glands
• seminiferous tubule degeneration is seen by 4 weeks of age (J:186144)

Mouse Models of Human Disease
OMIM IDRef(s)
Ovarian Cancer 167000 J:186144


Mouse Genome Informatics
cn128
    Ctnnb1tm1Mmt/Ctnnb1+
Krastm4Tyj/Kras+
Tg(Upk2-cre)6Xrw/0

involves: 129S4/SvJae * 129X1/SvJ * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis


Mouse Genome Informatics
cn129
    Krastm4Tyj/Kras+
Ptentm1Hwu/Pten+
Tg(Pdx1-cre)89.1Dam/0

involves: 129S4/SvJae * BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mutants exhibit accelerated development of acinar-to-ductal metaplasia, malignant pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma compared to single heterozygous Kras mutants, with almost 100% of mutants succumbing to cancer by 12 months of age
• 21 of 25 mice alive past 2 months of age develop well-to-moderately differentiated invasive ductal cancers
• rare metastasis to lungs is seen
• at 3 months of age, 8 of 12 mutants show development of pancreatic ductal adenocarcinoma (PDAC), and all mice show PDAC by 6 months of age
• loss of Pten heterozygosity is seen during pancreatic ductal adenocarcinoma progression but not in mPanIN lesions
• mutants show malignant pancreatic intraepithelial neoplasia (mPanIN) development starting at 1 month of age, and all show mPanIN by 3 months of age

mortality/aging
• median survival time is about 3.5 months

endocrine/exocrine glands
• acinar-to-ductal metaplasia is seen at 1-3 months of age, concentrated in the transition zone between morphologically normal pancreatic structures and mPanIN and PDAC lesions
• acinar-to-ductal metaplasia development precedes mPanIN formation
• metaplastic lesions show an increase in CD44+ cells

Mouse Models of Human Disease
OMIM IDRef(s)
Pancreatic Cancer 260350 J:164210


Mouse Genome Informatics
cn130
    Krastm4Tyj/Kras+
Tg(Mx1-cre)1Cgn/?

involves: 129S4/SvJae * BALB/c * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survival for around 35 days after pI-pC treatment
• survival of around 58 days even without pI-pC treatment

tumorigenesis
• nodules in lungs
• thymic T-cell lymphomas
• squamous papillomas

growth/size
• becoming emaciated

hematopoietic system
• develop lethal hematopoietic disease
• average hematocrit of 27%
• leukocytosis, usually involving increases in granulocytes
• myeloproliferative phenotype
• myeloid hyperplasia of bone marrow
• expansion of red pulp in spleen by granulocyte/monocyte lineages in 11 out of 16 cases
• erythroid expansion was seen in red pulp of spleen in 5 of 16 cases

immune system
• leukocytosis, usually involving increases in granulocytes
• myeloproliferative phenotype
• myeloid hyperplasia of bone marrow

liver/biliary system
• perivascular and periportal infiltration in liver by myeloid and erythroid cells similar to what is seen in spleen

integument
• ruffled fur


Mouse Genome Informatics
cn131
    Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu
Tg(Pdx1-cre)89.1Dam/0

involves: 129S4/SvJae * BALB/c * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• all mutants develop pancreatic ductal adenocarcinoma by 3 weeks of age

endocrine/exocrine glands
• mutants exhibit acinar-to-ductal metaplasia
• mutants show severe exocrine pancreatic atrophy and edema along with the presence of mPanINs, metaplasias, and ducto-insular complexes and pancreatic ductal adenocarcinoma at P17

homeostasis/metabolism
• pancreas at P1-P17 shows edema

mortality/aging
• mutants are moribound by weaning, with a median survival of about 17 days

digestive/alimentary system
• mutants show severe exocrine pancreatic atrophy and edema along with the presence of mPanINs, metaplasias, and ducto-insular complexes and pancreatic ductal adenocarcinoma at P17

Mouse Models of Human Disease
OMIM IDRef(s)
Pancreatic Cancer 260350 J:164210


Mouse Genome Informatics
cn132
    Krastm4Tyj/Kras+
Ptentm1Hwu/Pten+
Tg(Gfap-cre)77.6Mvs/0

involves: 129S4/SvJae * BALB/c * C57BL/6NHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survival is on average 22 weeks

tumorigenesis
• mutants develop multiple visible subcutaneous tumors with 100% penetrance, starting from 4 months of age
• majority of tumors are located on the back and sides
• each mutant has more than one lesion with features of human neurofibroma and malignant peripheral nerve sheath tumor
• progressive development of malignant peripheral nerve sheath tumors (MPNST) from neurofibroma, with 100% of mutants showing MPNST when followed for 7 months
• Pten loss of heterozygosity in mutants correlates with MPNST transformation from neurofibromas

Mouse Models of Human Disease
OMIM IDRef(s)
Neurofibromatosis, Type I; NF1 162200 J:154673


Mouse Genome Informatics
cn133
    Krastm4Tyj/Kras+
Tg(Tek-cre)12Flv/0

involves: 129S4/SvJae * C3H * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
N
• mutants show normal vascularization of the yolk sac and placental labyrinth (J:119477)


Mouse Genome Informatics
cn134
    Krastm4Tyj/Kras+
Tg(MUC1)79.24Gend/0

involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• following injection of a cre adenovirus in the ovarian bursa, all mice develop ovarian lesions consisting of endometrial glandular epithelium unlike un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice (J:154046)

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
• following injection of a cre adenovirus in the ovarian bursa, mice exhibit an increase in the anti-MUC1 IgG response compared with un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice
• following injection of a cre adenovirus in the ovarian bursa, mice exhibit an increase in MUC1-specific IgM unlike un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice and similarly treated Tg(MUC1)79.24Gend mice
• following injection of a cre adenovirus in the ovarian bursa, T cells in the spleen and regional lymph nodes exhibit decreased IFN-gamma in response to polyclonal stimulation compared with un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice

hematopoietic system