Mouse Genome Informatics
cn1
    Trp53tm2Tyj/Trp53tm2Tyj
involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit very limited proliferation potential and undergo senescence sooner than control cells that become immortalized


Mouse Genome Informatics
cn2
    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
cellular
• ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit increased invasion compared with control cells that is not as severe as in similarly treated cells from Trp53tm1Brn homozygotes


Mouse Genome Informatics
cn3
    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
cn4
    Mettm1Sst/Mettm1Sst
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
cellular
N
• ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit reduced invasion compared with similarly treated cells from Trp53tm1Brn/Trp53tm2Tyj mice (J:175978)


Mouse Genome Informatics
cn5
    Trp53tm1Brn/Trp53tm1Brn
Trp53tm2Tyj/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
cellular
• ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit increased invasion compared with control cells that is not as severe as in similarly treated cells from Trp53tm1Brn homozygotes


Mouse Genome Informatics
cn6
    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
cn7
    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/body
• 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
cn8
    Braftm1.1Brd/Braf+
Tg(Vil-cre)997Gum/0
Trp53tm2Tyj/Trp53tm2Tyj

involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 56% of mice at 10-20 months
• invasiveness of cancers considerably increased
• 25% of cancerous mice have metastases


Mouse Genome Informatics
cn9
    Krastm4Tyj/Kras+
Trp53tm2Tyj/Trp53+
Tg(Pdx1-cre)6Tuv/0

involves: 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
mortality/aging

tumorigenesis
• all but one mouse, develop large, firm, fibrotic head of the pancreas tumors
• metastatic foci spread to the surface of the liver, lungs, diaphragm, and adrenals with occasional metastasis to the peripancreatic, mesenteric, and retroperitoneal lymph nodes
• mice exhibit the full spectrum of preinvasive lesions
• some tumors are minor, poorly differentiated, or undifferentiated with anaplastic or sarcomatoid features
• some mice exhibit esophageal papillomas and hyperplasias or papillomatosis of the biliary tree unlike control mice

liver/biliary system

homeostasis/metabolism
• hemorrhagic

cellular
• in tumor cells

growth/size/body

digestive/alimentary system
• mice frequently exhibit small bowel obstructions unlike control mice

Mouse Models of Human Disease
OMIM IDRef(s)
Pancreatic Cancer 260350 J:98936