Phenotypes Associated with This Genotype

Genotype
MGI:5013916

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten⁺; Tg(Pdx1-cre)89.1Dam/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

neoplasm

increased pancreas tumor incidence ( J:164210 )

• 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

increased pancreatic ductal adenocarcinoma incidence ( J:164210 )

• 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

increased pancreatic intraepithelial neoplasia incidence ( J:164210 )

• 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

premature death ( J:164210 )

• median survival time is about 3.5 months

endocrine/exocrine glands

increased pancreas tumor incidence ( J:164210 )

• 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

increased pancreatic ductal adenocarcinoma incidence ( J:164210 )

• 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

increased pancreatic intraepithelial neoplasia incidence ( J:164210 )

• mutants show malignant pancreatic intraepithelial neoplasia (mPanIN) development starting at 1 month of age, and all show mPanIN by 3 months of age

pancreatic acinar-to-ductal metaplasia ( J:164210 )

• 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		DO ID	OMIM ID(s)	Ref(s)
pancreatic carcinoma		DOID:4905	OMIM:260350	J:164210