Mouse Genome Informatics
hm1
    Krastm1Bbd/Krastm1Bbd
involves: 129S1/Sv * 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
• homozygous embryos die at midgestation similar to Krastm1Tyi


Mouse Genome Informatics
cn2
    Krastm1Bbd/Kras+
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 50% survival at 40 weeks of age following intratracheal instillation of Ad-Cre
• following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), 50% of mice die by 40 weeks

tumorigenesis
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre)

Mouse Models of Human Disease
OMIM IDRef(s)
Lung Cancer 211980 J:172200


Mouse Genome Informatics
cn3
    Krastm1Bbd/Kras+
Mapk3tm1Gpg/Mapk3tm1Gpg

involves: 129/Sv * 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 50% survival at 46.3 weeks of age is seen following intratracheal instillation of Ad-Cre, a 20% increase in survival compared to single Kras mutants

tumorigenesis
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes


Mouse Genome Informatics
cn4
    Krastm1Bbd/Kras+
Mapk1tm1.1Hed/Mapk1tm1.1Hed
Mapk3tm1Gpg/Mapk3tm1Gpg

involves: 129/Sv * 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), mutants show 50% survival at 63 weeks versus 48 weeks in single Kras mutants, a 40% increase in survival

tumorigenesis
• 6 months following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), only a few tumors are observed; tumors that are found express normal levels of Mapk1


Mouse Genome Informatics
cn5
    Krastm1Bbd/Kras+
Map2k2tm1Chrn/Map2k2tm1Chrn

involves: 129/Sv * 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Ad-Cre treated mutants show 50% survival at 52 weeks compared to 45 weeks in single Kras heterozygous controls, indicating a slight 19% increase in survival

tumorigenesis
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes


Mouse Genome Informatics
cn6
    Krastm1Bbd/Kras+
Map2k1tm1Chrn/Map2k1tm1Chrn
Map2k2tm1Chrn/Map2k2tm1Chrn

involves: 129/Sv * 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Ad-Cre treated mice show 50% survival at 57 weeks of age compared to 33 weeks of age in single Kras heterozygous controls, indicating an almost 100% increase in survival

tumorigenesis
• 6 months following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), only a few tumors are observed; tumors that are present carry unrecombined Map2k1 alleles and express normal levels of Map2k1


Mouse Genome Informatics
cn7
    Krastm1Bbd/Kras+
Raf1tm2Bacc/Raf1tm2Bacc

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), mice show 50% survival at 63 weeks compared to 38 weeks in single Kras heterozygous controls, indicating an 83% increase in survival

tumorigenesis
• tumor burden is reduced compared to single Kras heterozygotes; tumors that are found express Raf1


Mouse Genome Informatics
cn8
    Krastm1Bbd/Kras+
Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd
Raf1tm2Bacc/Raf1tm2Bacc

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• primary mouse embryonic fibroblasts exposed to 4OHT for 5 days to activate cre/ERT2 recombinase exhibit decreased proliferation compared to single Kras heterozygotes


Mouse Genome Informatics
cn9
    Braftm1Sva/Braftm1Sva
Krastm1Bbd/Kras+
Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd
Raf1tm2Bacc/Raf1tm2Bacc

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• primary mouse embryonic fibroblasts exposed to 4OHT for 5 days to activate cre/ERT2 recombinase exhibit decreased proliferation that is similar to that in single Kras mutants without further additive effects


Mouse Genome Informatics
cn10
    Krastm1Bbd/Kras+
Trp53tm1Brd/Trp53+
Tg(Cela1-tTA)#Eps/?
Tg(tetO-cre)3Jig/?

involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 50% mortality by 6 months of age
• 100% mortality by 1 year of age

tumorigenesis
• metastases develop affecting liver, diaphragm, lungs, lymph nodes, and spleen
• all mice develop moderately to poorly differentiated pancreatic ductal adenocarcinomas, peritoneal explants, and perineural extensions

Mouse Models of Human Disease
OMIM IDRef(s)
Pancreatic Cancer 260350 J:119988


Mouse Genome Informatics
cn11
    Cdk4tm2Bbd/Cdk4tm2Bbd
Krastm1Bbd/Krastm1Bbd
Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• tamoxifen-treated mice exhibit reduced tumor burden and tumor grade compared with similarly treated Krastm1Bbd/Kras+ Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd mice


Mouse Genome Informatics
cn12
    Cdk2tm2Sgo/Cdk2tm2Sgo
Krastm1Bbd/Krastm2Bbd
Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• tamoxifen-treated mice exhibit an increase in lifespan compared with similarly treated Krastm1Bbd/Kras+ Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd littermates

tumorigenesis
• tamoxifen-treated mice exhibit reduced tumor burden and tumor grade compared with similarly treated Krastm1Bbd/Kras+ Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd mice


Mouse Genome Informatics
cn13
    Krastm1Bbd/Krastm2Bbd
Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 50% survival for tamoxifen-treated mice is 25 weeks compared with 42 weeks for similarly treated Krastm1Bbd/Kras+ Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd littermates

tumorigenesis
• lung tumors in tamoxifen-treated mice are more aggressive than in similarly treated Krastm1Bbd/Kras+ Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd mice
• however, treatment with the Cdk4 inhibitor PD0332991 reduces tumor formation
• in mice treated with tamoxifen

cellular
• proliferation of lung cells in tamoxifen-treated mice exhibit 8- to 10-fold greater proliferation than in Cdk4tm2.1Bbd/Cdk4tm2.1Bbd Krastm1Bbd/Krastm2Bbd Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd mice

Mouse Models of Human Disease
OMIM IDRef(s)
Lung Cancer Susceptibility 3; LNCR3 612571 J:161780


Mouse Genome Informatics
cn14
    Cdk4tm2.1Bbd/Cdk4tm2.1Bbd
Krastm1Bbd/Krastm2Bbd
Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• lung cells in tamoxifen-treated mice exhibit 8- to 10-fold reduction in proliferation and early senescence compared to in similarly treated Krastm1Bbd/Krastm2Bbd Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd mice
• tamoxifen-treated mice exhibit adenocarcinomas that are not as severe as in Krastm1Bbd/Krastm2Bbd Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd mice

cellular
• proliferation of lung cells in tamoxifen-treated mice exhibit 8- to 10-fold less proliferation than in similarly treated Krastm1Bbd/Krastm2Bbd Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd mice
• tamoxifen-treated mice exhibit increased cell replicative senescence in the lungs compared to in similarly treated Krastm1Bbd/Krastm2Bbd Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd mice


Mouse Genome Informatics
cn15
    Cdk4tm2Bbd/Cdk4tm2.1Bbd
Krastm1Bbd/Krastm2Bbd
Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• tamoxifen-treated mice infected with a flp-expressing adenovirus exhibit decreased proliferation and early senescence of tumor cells compared with tamoxifen and infected with GFP-expressing adenovirus
• tamoxifen-treated mice infected with a flp-expressing adenovirus exhibit reduced lesions compared to in mice treated with tamoxifen and infected with GFP-expressing adenovirus
• in tamoxifen-treated mice as in similarly treated Krastm1Bbd/Krastm2Bbd Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd mice

cellular
• tamoxifen-treated mice infected with a flp-expressing adenovirus exhibit early senescence of tumor cells compared with tamoxifen and infected with GFP-expressing adenovirus
• tamoxifen-treated mice infected with a flp-expressing adenovirus exhibit decreased proliferation of tumor cells compared with tamoxifen and infected with GFP-expressing adenovirus


Mouse Genome Informatics
cn16
    Krastm1Bbd/Kras+
Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• the mean lifespan of mice treated tamoxifen is 34-42 weeks

tumorigenesis
• in mice treated with tamoxifen at weaning
• in mice treated with tamoxifen at weaning

Mouse Models of Human Disease
OMIM IDRef(s)
Lung Cancer Susceptibility 3; LNCR3 612571 J:161780


Mouse Genome Informatics
cn17
    Cdk6tm1Bbd/Cdk6tm1Bbd
Krastm1Bbd/Kras+
Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 50% of tamoxifen-treated mice survive at 40 weeks

tumorigenesis
• in mice treated with tamoxifen at weaning
• in mice treated with tamoxifen at weaning

Mouse Models of Human Disease
OMIM IDRef(s)
Lung Cancer Susceptibility 3; LNCR3 612571 J:161780


Mouse Genome Informatics
cn18
    Cdk2tm1Sgo/Cdk2tm1Sgo
Krastm1Bbd/Kras+
Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice treated tamoxifen at weaning exhibit an increase in lifespan of 8 weeks (42 weeks) compared with similarly treated Krastm1Bbd/Kras+ Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd littermates (34 weeks)

tumorigenesis
• tamoxifen-treated mice exhibit reduced tumor burden compared with similarly treated Krastm1Bbd/Kras+ Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd mice


Mouse Genome Informatics
cn19
    Krastm1Bbd/Kras+
Mapk1tm1.1Hed/Mapk1tm1.1Hed

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 50% survival at 34.9 weeks versus 31.2 weeks in single Kras mutants following intratracheal instillation of Ad-Cre, indicating a 16% increase in survival

tumorigenesis
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes


Mouse Genome Informatics
cn20
    Krastm1Bbd/Kras+
Map2k1tm1Chrn/Map2k1tm1Chrn

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), mutants show 50% survival at 44 weeks compared to 37.5 weeks in single Kras heterozygous controls, indicating a slight 22% increase in survival

tumorigenesis
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes


Mouse Genome Informatics
cn21
    Braftm1Sva/Braftm1Sva
Krastm1Bbd/Kras+

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), mice show 50% survival at 41.5 weeks compared to 40 weeks in single Kras heterozygous controls, indicating similar survival

tumorigenesis
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes


Mouse Genome Informatics
cn22
    Braftm1Sva/Braftm1Sva
Krastm1Bbd/Kras+
Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• primary mouse embryonic fibroblasts exposed to 4OHT for 5 days to activate cre/ERT2 recombinase exhibit decreased proliferation compared to single Kras heterozygotes


Mouse Genome Informatics
cn23
    Krastm1Bbd/Kras+
Tg(CMV-cre)1Cgn/?

involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• double mutants develop breathing difficulties after 7 - 8 months of age
• frequent embryonic lethality; however, a significant number of double mutants survive

tumorigenesis
• a large spectrum of multifocal lesions are seen in the lung including; small patches of bronchiolo-alveolar hyperplasias to large bronchiolo-alveolar adenomas that compress adjacent lung structures and appear to derive from type II pneumocytes
• large bronchiolo-alveolar adenocarcinomas that compress adjacent lung structures and appear to derive from type II pneumocytes
• histiocytic sarcoma and other sarcomas seen in 2 out of 20 and 3 out of 20 double mutants, respectively
• anal papillomas seen in 3 out of 20 double mutants

cellular
• MEFs expressing the oncogenic protein do not undergo proliferative senescence and proliferate continuously as immortal cells

respiratory system
• double mutants develop breathing difficulties after 7 - 8 months of age


Mouse Genome Informatics
cn24
    Cdk4tm1.1Bbd/Cdk4+
Krastm1Bbd/Kras+
Tg(CMV-cre)1Cgn/?

involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• latency to develop lung adenomas is significantly shorter compared to double mutants wild-type for Cdk4; however development of tumors characteristic of Cdk4tm1.1Bbd mutant mice is not accelerated
• histiocytic sarcoma and other sarcomas are seen
• anal papillomas are seen

digestive/alimentary system
• focal metaplasia in the pancreatic ducts consisting of tall columnar cells with abundant apical mucin resembling gastric surface epithelial cells

endocrine/exocrine glands
• focal metaplasia in the pancreatic ducts consisting of tall columnar cells with abundant apical mucin resembling gastric surface epithelial cells


Mouse Genome Informatics
cn25
    Fntbtm1Bbd/Fntbtm1Bbd
Krastm1Bbd/Kras+
Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• after treatment with 4-hydroxy-tamoxifen for 24 weeks multiple lung adenomas develop by 7 months of age; however no difference in the latency, number, or size of tumors was seen compared to double mutants wild-type for Fntb
• after treatment with 4-hydroxy-tamoxifen for 24 weeks multiple lung adenocarcinomas develop by 7 months of age; however no difference in the latency, number, or size of tumors was seen compared to double mutants wild-type for Fntb


Mouse Genome Informatics
cn26
    Krastm1Bbd/Kras+
Mapk14tm1Nbr/Mapk14tm2Nbr
Polr2atm1(cre/ERT2)Bbd/Polr2a+

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die before week 32 due to increased lung cancer progression

respiratory system
• lung differentiation is abnormal with increased SP-C-positive cells
• 20 weeks after treatment, lungs are increased in size

tumorigenesis
• mice also have tumors in the thymus and organs such as kidney and liver by 24 weeks after treatment whereas controls only have tumors in lungs and thymus
• 2 weeks after 5-hydroxytamoxifen treatment, small tumors are found in the lungs
• 20 weeks after treatment, lungs are oversized with 2-3 times as many tumors, many often >2mm in diameter, while lungs of Kras, Mapk14 heterozygotes have normal lungs with fewer, smaller tumors; tumors in Mapk14 homozygotes are more poorly differentiated and have higher mitotic indices
• at 26 weeks, total tumor number is slightly higher than in controls with much higher numbers of tumors larger than 2 mm in diameter and a higher ratio of lung mass to total mass
• tumors are detected 2 weeks after 5-hydroxytamoxifen treatment and after 4 weeks, clear signs of adenomas are present in most lungs compared to only a few small adenomas in lungs of treated Kras, Mapk14tm2Nbr/+ control mice
• adenocarcinomas are detected at 15 weeks but not in controls


Mouse Genome Informatics
cn27
    Krastm1Bbd/Kras+
Mapk14tm2Nbr/Mapk14+
Polr2atm1(cre/ERT2)Bbd/Polr2a+

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice live up to 40 weeks

tumorigenesis
• by 24 weeks, mice develop tumors in the thymus
• by 24 weeks, mice develop tumors in lungs
• at 4 weeks after 5-hydroxytamoxifen treatment, a few small adenomas are observed in some animals


Mouse Genome Informatics
cn28
    Krastm1Bbd/Kras+
Tg(Pbsn-cre)4Prb/0

involves: 129S1/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
reproductive system
• at 200 days, 100% of mice exhibit atypical hypoplasia unlike wild-type mice (J:143034)
• at 500 days, 93% of mice exhibit atypical hypoplasia unlike wild-type mice (J:143034)

tumorigenesis
• in 7% of mice at 500 days (J:143034)
• at 200 days, 67% of mice develop prostate intraepithelial neoplasia that display foci of small solid and cribiform intraluminal proliferation of atypical cells and nuclear atypia unlike wild-type mice (J:143034)
• at 500 days, 60% of mice exhibit prostate intraepithelial neoplasia unlike in wild-type mice (J:143034)

endocrine/exocrine glands
• at 200 days, 100% of mice exhibit atypical hypoplasia unlike wild-type mice (J:143034)
• at 500 days, 93% of mice exhibit atypical hypoplasia unlike wild-type mice (J:143034)

Mouse Models of Human Disease
OMIM IDRef(s)
Prostate Cancer 176807 J:143034


Mouse Genome Informatics
cn29
    Ctnnb1tm1Mmt/Ctnnb1+
Krastm1Bbd/Kras+
Tg(Pbsn-cre)4Prb/0

involves: 129S1/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
• mice die prior to day 300

reproductive system
• mice exhibit keratinized squamous metaplasia in the bulbourethral gland unlike wild-type mice (J:143034)

tumorigenesis
• all mice develop diffuse, locally invasive carcinomas in the prostate that develop from solid or sheet-like proliferation with occasional rosette structures, nuclear atypia, apoptotic bodies, and mitosis unlike in wild-type mice (J:143034)

renal/urinary system
• mice exhibit keratinized squamous metaplasia in the urethral gland unlike wild-type mice

endocrine/exocrine glands
• mice exhibit keratinized squamous metaplasia in the bulbourethral gland unlike wild-type mice (J:143034)


Mouse Genome Informatics
cn30
    Krastm1Bbd/Kras+
Tg(CMV-cre/ERT)1Ipc/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• double mutants treated with 4-hydroxy-tamoxifen at 10 days of age develop breathing difficulties after 7 - 8 months of age

tumorigenesis
• after treatment with 4-hydroxy-tamoxifen at 10 days of age, a large spectrum of multifocal lesions are seen in the lung at 7-8 months of age including; small patches of bronchiolo-alveolar hyperplasias to large bronchiolo-alveolar adenomas that compress adjacent lung structures and appear to derive from type II pneumocytes
• after treatment with 4-hydroxy-tamoxifen at 10 days of age, at 7-8 months of age large bronchiolo-alveolar adenocarcinomas that compress adjacent lung structures and appear to derive from type II pneumocytes are seen

cellular
• MEFs expressing the oncogenic protein do not undergo proliferative senescence and proliferate continuously as immortal cells

respiratory system
• double mutants treated with 4-hydroxy-tamoxifen at 10 days of age develop breathing difficulties after 7 - 8 months of age

endocrine/exocrine glands
• hyperplastic Harderian gland seen in double mutants treated with 4-hydroxy-tamoxifen at 10 days of age


Mouse Genome Informatics
cn31
    Krastm1Bbd/Krastm1Bbd
Tg(Cela1-tTA)#Eps/?
Tg(tetO-cre)3Jig/?

involves: 129S1/Sv * 129X1/SvJ * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• focal morphological lesions develop in acinar and centroacinar cells at 1-3 months
• acinar to ductal metaplasias develop
• some mice develop ductal adenocarcinomas by 12 months
• properties are similar to those in human patients
• sometimes areas of non malignant hyperplasia develop
• latency is increased if gene expression is delayed by maintaining exposure to doxycycline until 10 days of age
• if doxycycline exposure continues to 2 months of age, no pancreatic abnormalities develop

Mouse Models of Human Disease
OMIM IDRef(s)
Pancreatic Cancer 260350 J:119988