Phenotypes Associated with This Genotype

Genotype
MGI:3840644

• Allelic Composition: Abcb4^tm1Bor/Abcb4^tm1Bor
• Genetic Background: FVB.129P2-Abcb4^tm1Bor/J

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

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:100491 )

N • mice exhibit normal plasma levels of sitosterol and campesterol

increased circulating bilirubin level ( J:105357 , J:217802 )

• slight increase (J:105357)

• Background Sensitivity: total bilirubin in serum of aged mice on the FVB/N background is lower at 7 months of age compared to mice on the BALB/cAnNCrl background (J:217802)

abnormal circulating enzyme level ( J:105357 )

• elevated serum transaminase levels

increased circulating alanine transaminase level ( J:100491 , J:217802 )

• increase in serum alanine aminotransferase is similar on both the BALB/cAnNCrl and FVB/N backgrounds (J:217802)

increased circulating alkaline phosphatase level ( J:105357 , J:217802 )

• Background Sensitivity: serum levels of alkaline phosphatase are lower on the FVB/N background and show a decrease in levels by 12 weeks compared to mice on the BALB/cAnNCrl background in which levels increase with age (J:217802)

increased circulating aspartate transaminase level ( J:100491 , J:217802 )

• increase in serum aspartate aminotransferase is similar on both the BALB/cAnNCrl and FVB/N backgrounds (J:217802)

cardiovascular system

portal hypertension ( J:217802 )

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

• Background Sensitivity: portal pressure in mice on the FVB/N background increases at a slower pace compared to mice on the BALB/cAnNCrl background

liver/biliary system

portal hypertension ( J:217802 )

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

• Background Sensitivity: portal pressure in mice on the FVB/N background increases at a slower pace compared to mice on the BALB/cAnNCrl background

abnormal bile duct morphology ( J:105357 )

• mice exhibit proliferation of bile ducts, accompanied by periportal and periductal fibrosis, resulting in fibro-obliteration and segmental strictures of bile duct

• 42% of 7-10 month old females, but not males, develop choledocholithiasis (bile duct stones)

dilated bile duct ( J:105357 )

♀ • dilated extrahepatic duct in 7 month old females

abnormal gallbladder size ( J:105357 )

• gallbladders are 3 times larger than in wild-type mice at 9 weeks of age

• over time, gallbladder size decreases in males, but not females, such that at 18 weeks of age, some males at 18 weeks of age have very small gallbladders filled with sticky mucin gel and needle-like crystals

bile duct inflammation ( J:105357 )

• progressive sclerosing cholangitis

gallstones ( J:105357 )

• 50% and 80% of females at 12 and 15 weeks of age, respectively, exhibit gallstones in the gallbladder biles and by 18 weeks, all females have gallstones

• males form gallstones later, after 15 weeks of age, and with lower prevalence rates than in females

• core of stones are composed of needle-like crystals and gelled mucin

• number of gallstones per mouse ranges from 1-8 with an average of 1.3 +/- 0.3 stones per mouse and most gallstones are smaller than 0.1 mm

• stone number and size are higher in females than males

• 42% of 7-10 month old females, but not males, develop choledocholithiasis

abnormal liver morphology ( J:105357 )

• cholestatic liver damage

• mature mice develop intrahepatic stones, which are composed of needle-like crystals like the gallbladder stones

enlarged liver ( J:105357 )

liver cirrhosis ( J:217802 )

• Background Sensitivity: mice on the FVB/N background show slower development of cirrhosis compared to mice on the BALB/cAnNCrl 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 FVB/N background show slower progression of liver fibrosis compared to mice on the BALB/cAnNCrl background

• Background Sensitivity: collagen content in the liver of mice on the FVB/N background is lower at any time point studied compared to mice on the BALB/cAnNCrl background

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

• Background Sensitivity: females exhibit more severe fibrosis than males

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

• prominent sinusoidal fibrosis starting at 8 weeks of age

increased hepatocellular carcinoma incidence ( J:217802 )

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

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

• liver tumors are classified as hepatocellular carcinoma

intrahepatic cholestasis ( J:105357 )

• occluded intrahepatic bile ducts filled with crystalline occlusions composed of needle-like crystals and mucin gel

abnormal bile composition ( J:100491 , J:105357 )

• bile cholesterol levels are decreased compared to in wild-type mice (J:100491)

• gallbladder bile precipitates solid crystals, with males forming these needle-like crystals later (after 15 weeks) than females (after 12 weeks of age) and with a lower prevalence than in females (J:105357)

• 33% and 60% of females at 12 and 15 weeks of age, respectively, exhibit needle-like crystals in the gallbladder biles (J:105357)

• phosphatidylcholine (PC) concentrations in the gallbladder biles are decreased, and the relative compositions shift to greater proportions of the more hydrophobic PC-(18:0-18:2) and PC-(18:0-20:4) (J:105357)

• females exhibit a more hydrophobic bile salt pool due to lower tauro-beta-muricholate levels in bile (J:105357)

hematopoietic system

enlarged spleen ( J:217802 )

neoplasm

increased hepatocellular carcinoma incidence ( J:217802 )

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

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

• liver tumors are classified as hepatocellular carcinoma

digestive/alimentary system

abnormal feces composition ( J:100491 )

• fecal acidic sterol levels are decreased 30% compared to in wild-type mice

• however, fecal neutral sterol levels are normal

endocrine/exocrine glands

abnormal bile duct morphology ( J:105357 )

• mice exhibit proliferation of bile ducts, accompanied by periportal and periductal fibrosis, resulting in fibro-obliteration and segmental strictures of bile duct

• 42% of 7-10 month old females, but not males, develop choledocholithiasis (bile duct stones)

dilated bile duct ( J:105357 )

♀ • dilated extrahepatic duct in 7 month old females

abnormal gallbladder size ( J:105357 )

• gallbladders are 3 times larger than in wild-type mice at 9 weeks of age

• over time, gallbladder size decreases in males, but not females, such that at 18 weeks of age, some males at 18 weeks of age have very small gallbladders filled with sticky mucin gel and needle-like crystals

immune system

enlarged spleen ( J:217802 )

bile duct inflammation ( J:105357 )

• progressive sclerosing cholangitis

growth/size/body

enlarged liver ( J:105357 )

enlarged spleen ( J:217802 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cholecystitis		DOID:1949	OMIM:600803	J:105357