Phenotypes Associated with This Genotype

Genotype
MGI:5659501

• Allelic Composition: Abcb4^tm1Bor/Abcb4^tm1Bor
• Genetic Background: CAnNCrl.12P2(FVB)-Abcb4^tm1Bor

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

liver/biliary system

portal hypertension ( J:217802 )

• Background Sensitivity: mice on the BALB/cAnNCrl background show an earlier onset of severe portal hypertension than mice on the FVB/N background

• Background Sensitivity: portal pressure in mice on the BALB/cAnNCrl background increases at a higher pace compared to mice on the FVB/N background, peaking at 12 mmHg at 12 weeks compared to 8.2 mmHg in mice on the FVB/N background

liver cirrhosis ( J:217802 )

• Background Sensitivity: mice on the BALB/cAnNCrl background show accelerated development of cirrhosis compared to mice on the FVB/N background

liver fibrosis ( J:217802 )

• mice spontaneously develop periductal onion-skin type fibrotic lesions starting from 4 weeks of age

• Background Sensitivity: mice on the BALB/cAnNCrl background show accelerated liver fibrosis compared to mice on the FVB/N background, with signs of bridging fibrosis already at 8 weeks and thick septae formation by 12 weeks

• Background Sensitivity: collagen content in the liver of mice on the BALB/cAnNCrl background is higher at any time point studied compared to mice on the FVB/N background, with total hydroxyproline content about 3-fold higher in the liver than in mice on the FVB/N background

• Background Sensitivity: fibrotic matrix in mice on the BALB/cAnNCrl background is cross-linked to a greater degree than in mice on the FVB/N background

• Background Sensitivity: males exhibit more severe fibrosis than females

• Background Sensitivity: marker analysis indicates that fibrogenic cell activation is amplified in mice on the BALB/cAnNCrl background compared to the FVB/N background

• prominent sinusoidal fibrosis starting at 8 weeks of age

increased hepatocellular carcinoma incidence ( J:217802 )

• Background Sensitivity: mice on the BALB/cAnNCrl background show accelerated development of primary liver cancer compared to mice on the FVB/N background, showing tumors starting at 7 months of age compared to 12 months of age on the FVB/N background

• Background Sensitivity: tumor burden in mice on the BALB/cAnNCrl background is higher than on the FVB/N background

• liver tumors are classified as hepatocellular carcinoma

neoplasm

increased hepatocellular carcinoma incidence ( J:217802 )

• Background Sensitivity: mice on the BALB/cAnNCrl background show accelerated development of primary liver cancer compared to mice on the FVB/N background, showing tumors starting at 7 months of age compared to 12 months of age on the FVB/N background

• Background Sensitivity: tumor burden in mice on the BALB/cAnNCrl background is higher than on the FVB/N background

• liver tumors are classified as hepatocellular carcinoma

cardiovascular system

portal hypertension ( J:217802 )

• Background Sensitivity: mice on the BALB/cAnNCrl background show an earlier onset of severe portal hypertension than mice on the FVB/N background

• Background Sensitivity: portal pressure in mice on the BALB/cAnNCrl background increases at a higher pace compared to mice on the FVB/N background, peaking at 12 mmHg at 12 weeks compared to 8.2 mmHg in mice on the FVB/N background

growth/size/body

weight loss ( J:217802 )

• mice lose weight at 12 months of age with a 21.5% reduction in weight compared to 2.9% in wild-type mice

enlarged spleen ( J:217802 )

hematopoietic system

enlarged spleen ( J:217802 )

homeostasis/metabolism

increased circulating bilirubin level ( J:217802 )

• Background Sensitivity: total bilirubin in serum of aged mice on the BALB/cAnNCrl background is higher at 7 months of age compared to mice on the FVB/N background, and continues to increase through 12 months of age

increased circulating alanine transaminase level ( J:217802 )

• increase in serum alanine aminotransferase is similar on both the BALB/cAnNCrl and FVB/N backgrounds

increased circulating alkaline phosphatase level ( J:217802 )

• Background Sensitivity: serum levels of alkaline phosphatase are higher on the BALB/cAnNCrl background and increase with age compared to mice on the FVB/N background which show a decrease in levels by 12 weeks

increased circulating aspartate transaminase level ( J:217802 )

• increase in serum aspartate aminotransferase is similar on both the BALB/cAnNCrl and FVB/N backgrounds

immune system

enlarged spleen ( J:217802 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
primary sclerosing cholangitis		DOID:0060643	OMIM:613806	J:217802