Phenotypes Associated with This Genotype

Genotype
MGI:2653844

• Allelic Composition: Abcb4^tm1Bor/Abcb4^tm1Bor
• Genetic Background: either: (involves: 129P2/OlaHsd) or (involves: 129P2/OlaHsd * FVB/N)

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

reproductive system

reduced female fertility ( J:21232 )

♀ • at 4 months

liver/biliary system

abnormal hepatobiliary system morphology ( J:21232 )

abnormal bile duct morphology ( J:15531 )

• portal expansion due to ductular proliferation is seen

bile duct proliferation ( J:21232 )

• mice exhibit ductular proliferation and portal inflammation with mixed inflammatory infiltrate unlike in wild-type mice

dilated bile duct ( J:15531 )

• larger bile ducts are dilated

enlarged liver ( J:21232 )

• beginning at 4 to 6 months

abnormal bile canaliculus morphology ( J:15531 , J:21232 )

• prominent widening and increased tortuosity of bile canaliculi with loss of microvilli is present (J:15531)

• bile canaliculi fail to mature remaining wide and smooth unlike in wild-type mice (J:21232)

abnormal hepatocyte morphology ( J:15531 )

• hepatocyte degeneration, irregular size with nuclear polymorphism and focal necrosis are observed, along with increased proliferation

abnormal portal triad morphology ( J:21232 )

• at 3 months, mice exhibit expansion of the portal triad unlike in wild-type mice

hepatic necrosis ( J:21232 )

• beginning at 4 to 6 months

increased hepatocellular carcinoma incidence ( J:21232 )

• beginning at 4 to 6 months, mice develop hepatocellular carcinoma with necrosis, hemorrhage, and strong cytonuclear polymorphism unlike in wild-type mice

• mice exhibit lung metastasis

abnormal hepatobiliary system physiology ( J:21232 )

liver hemorrhage ( J:21232 )

• beginning at 4 to 6 months

bile duct inflammation ( J:15531 , J:21232 )

• inflammation of bile ducts (J:15531)

liver inflammation ( J:15531 )

• portal inflammation with mixed inflammatory infiltrate and slight fibrosis

abnormal bile secretion ( J:15531 )

biliary cirrhosis ( J:21232 )

• at 3 months, mice exhibit biliary cirrhosis with porto-portal fibrous septa unlike in wild-type mice

cholestasis ( J:21232 )

intrahepatic cholestasis ( J:15531 )

• moderate liver damage with cholestatic properties (raised serum-conjugated bilirubin) is observed

abnormal bile composition ( J:15531 )

• absence of phospholipid secretion in bile, lipid secretion is decreased and there is a 15-reduction in cholesterol secretion in bile

• glutathione secretion in bile is ~14% of wild-type

• chloride secretion is slightly, but significantly, elevated

• phospolipid to bile salt ratio is only ~41% of wild-type

homeostasis/metabolism

abnormal blood homeostasis ( J:15531 )

• serum is yellowish, suggesting liver damage

abnormal circulating bilirubin level ( J:15531 )

• 12-fold elevated bilirubin level; ~50% of this is conjugated

abnormal circulating alanine transaminase level ( J:15531 )

• 5.8-fold increase in alanine transaminase level

abnormal circulating alkaline phosphatase level ( J:15531 )

• 3-fold increase in serum alkaline phosphatase level

abnormal circulating aspartate transaminase level ( J:15531 )

• 4-fold increase in aspartate transaminase level

neoplasm

increased hepatocellular carcinoma incidence ( J:21232 )

• beginning at 4 to 6 months, mice develop hepatocellular carcinoma with necrosis, hemorrhage, and strong cytonuclear polymorphism unlike in wild-type mice

• mice exhibit lung metastasis

immune system

bile duct inflammation ( J:15531 , J:21232 )

• inflammation of bile ducts (J:15531)

liver inflammation ( J:15531 )

• portal inflammation with mixed inflammatory infiltrate and slight fibrosis

endocrine/exocrine glands

abnormal bile duct morphology ( J:15531 )

• portal expansion due to ductular proliferation is seen

bile duct proliferation ( J:21232 )

• mice exhibit ductular proliferation and portal inflammation with mixed inflammatory infiltrate unlike in wild-type mice

dilated bile duct ( J:15531 )

• larger bile ducts are dilated

cardiovascular system

liver hemorrhage ( J:21232 )

• beginning at 4 to 6 months

growth/size/body

enlarged liver ( J:21232 )

• beginning at 4 to 6 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:21232