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Phenotypes Associated with This Genotype
Genotype
MGI:5013916
Allelic
Composition
Krastm4Tyj/Kras+
Ptentm1Hwu/Pten+
Tg(Pdx1-cre)89.1Dam/0
Genetic
Background
involves: 129S4/SvJae * BALB/c * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Krastm4Tyj mutation (8 available); any Kras mutation (37 available)
Ptentm1Hwu mutation (5 available); any Pten mutation (39 available)
Tg(Pdx1-cre)89.1Dam mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• 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
• 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

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
pancreatic carcinoma DOID:4905 OMIM:260350
J:164210


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
09/22/2020
MGI 6.16
The Jackson Laboratory