Phenotypes Associated with This Genotype

Genotype
MGI:4941336

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Trp53^tm2Tyj/Trp53⁺; Tg(Pdx1-cre)6Tuv/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * FVB/N

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

mortality/aging

premature death ( J:98936 )

decreased tumor-free survival time ( J:371968 )

• mice of this genotype (referred to as KPC mice, a model for pancreatic ductal adenocarcinoma) exhibit a median survival of 16 weeks; at 22 weeks, the overall survival rate is 0%

neoplasm

increased T cell derived lymphoma incidence ( J:98936 )

• in 2 mice

increased pancreatic ductal adenocarcinoma incidence ( J:98936 , J:371968 )

• all but one mouse, develop large, firm, fibrotic head of the pancreas tumors (J:98936)

• metastatic foci spread to the surface of the liver, lungs, diaphragm, and adrenals with occasional metastasis to the peripancreatic, mesenteric, and retroperitoneal lymph nodes (J:98936)

• mice exhibit the full spectrum of preinvasive lesions (J:98936)

• some tumors are minor, poorly differentiated, or undifferentiated with anaplastic or sarcomatoid features (J:98936)

increased pancreatic intraepithelial neoplasia incidence ( J:98936 )

• in young mice

abnormal tumor progression ( J:371968 )

• ACAA1 (acetyl-Coenzyme A acyltransferase 1A) protein levels are minimal in normal pancreatic tissue but increased 1.2-fold, 2.4-fold, and 2-fold during acinar-ductal epithelial degeneration (ADM), pancreatic intraepithelial neoplasia (PanIN), and pancreatic ductal adenocarcinoma (PDAC) stages, respectively, indicating a progressive increase during tumor development

• moreover, at the PDAC stage, ACOX1 (acyl-Coenzyme A oxidase 1, palmitoyl) protein expression is 5.92 times higher than in wild-type mice

increased teratocarcinoma incidence ( J:98936 )

• in one mouse

increased papilloma incidence ( J:98936 )

• some mice exhibit esophageal papillomas and hyperplasias or papillomatosis of the biliary tree unlike control mice

increased esophageal papilloma incidence ( J:98936 )

• in some mice

liver/biliary system

cholestasis ( J:98936 )

homeostasis/metabolism

abnormal fatty acid beta-oxidation ( J:371968 )

• KPC mice show a progressive increase in the expression of key proteins involved in fatty acid oxidation (FAO) within peroxisomes (ACAA1 and ACOX1) during PDAC development

hemorrhagic ascites ( J:98936 )

• hemorrhagic

cellular

chromosomal instability ( J:98936 )

• in tumor cells

abnormal fatty acid beta-oxidation ( J:371968 )

• KPC mice show a progressive increase in the expression of key proteins involved in fatty acid oxidation (FAO) within peroxisomes (ACAA1 and ACOX1) during PDAC development

growth/size/body

cachexia ( J:98936 )

distended abdomen ( J:98936 )

digestive/alimentary system

increased esophageal papilloma incidence ( J:98936 )

• in some mice

intestinal obstruction ( J:98936 )

• mice frequently exhibit small bowel obstructions unlike control mice

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:98936 )

• in 2 mice

increased pancreatic ductal adenocarcinoma incidence ( J:98936 , J:371968 )

• all but one mouse, develop large, firm, fibrotic head of the pancreas tumors (J:98936)

• metastatic foci spread to the surface of the liver, lungs, diaphragm, and adrenals with occasional metastasis to the peripancreatic, mesenteric, and retroperitoneal lymph nodes (J:98936)

• mice exhibit the full spectrum of preinvasive lesions (J:98936)

• some tumors are minor, poorly differentiated, or undifferentiated with anaplastic or sarcomatoid features (J:98936)

increased pancreatic intraepithelial neoplasia incidence ( J:98936 )

• in young mice

immune system

increased T cell derived lymphoma incidence ( J:98936 )

• in 2 mice

hematopoietic system

increased T cell derived lymphoma incidence ( J:98936 )

• in 2 mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pancreatic ductal adenocarcinoma		DOID:3498		J:98936