Phenotypes Associated with This Genotype

Genotype
MGI:5618809

• Allelic Composition: Abcb4^tm1Bor/Abcb4^tm1Bor; Por^tm1Wolf/Por^tm1Wolf; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA * FVB/N

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

endocrine/exocrine glands

bile duct proliferation ( J:215915 )

• mice fed a cholic acid-supplemented diet for 8 weeks exhibit bile duct proliferation

growth/size/body

growth/size/body region phenotype ( J:215915 )

N • mice fed a 0.03% cholic acid-supplemented diet directly from weaning exhibit normal growth

increased liver weight ( J:215915 )

• mice fed a cholic acid-supplemented diet for 8 weeks exhibit an increased liver to body weight ratio

cellular

increased hepatocyte proliferation ( J:215915 )

• mice fed a cholic acid-supplemented diet for 8 weeks exhibit increased hepatocyte proliferation

homeostasis/metabolism

increased circulating bilirubin level ( J:215915 )

• plasma bilirubin levels are mildly increased at weaning and are further increased after 8 weeks of 0.03% cholic acid-supplemented diet

increased circulating alanine transaminase level ( J:215915 )

• plasma alanine transaminase levels are strongly elevated after 8 weeks of cholic acid-supplemented diet

increased circulating alkaline phosphatase level ( J:215915 )

• plasma alkaline phosphatase levels are strongly elevated after 8 weeks of cholic acid-supplemented diet

abnormal bile salt homeostasis ( J:215915 )

• on a cholic acid-supplemented diet, plasma bile salts predominantly consist of about 90% taurocholate (TC) and about 7% tauro-beta-muricholate (TbetaMC) compared to about 60% TC and 23% TbetaMC in single Abcb4 homozygotes

• on a cholic acid-supplemented diet, biliary bile salts predominantly consist of about 90% TC and about 2.5% of the secondary bile salt taurochenodeoxycholate (TDC) compared to 75% TC and 20% TbetaMC in single Abcb4 homozygotes

• on a cholic acid-supplemented diet, the biliary hydrophobicity index, but not the plasma hydrophobicity index, is elevated, indicating a more hydrophobic biliary bile salt pool

• however, mice fed a cholic acid-supplemented diet for 8 weeks exhibit normal bile flow and biliary bile salt output

increased bile salt level ( J:215915 )

• plasma bile salt levels are strongly elevated after 8 weeks of cholic acid-supplemented diet

liver/biliary system

increased hepatocyte proliferation ( J:215915 )

• mice fed a cholic acid-supplemented diet for 8 weeks exhibit increased hepatocyte proliferation

bile duct proliferation ( J:215915 )

• mice fed a cholic acid-supplemented diet for 8 weeks exhibit bile duct proliferation

increased liver weight ( J:215915 )

• mice fed a cholic acid-supplemented diet for 8 weeks exhibit an increased liver to body weight ratio

liver fibrosis ( J:215915 )

• mice fed a regular diet exhibit portal fibrosis

• mice fed a cholic acid-supplemented diet for 8 weeks exhibit portal fibrosis that is more severe than in single Abcb4 homozygotes

cholestasis ( J:215915 )

• mice fed a cholic acid-supplemented diet for 8 weeks develop a severe cholestatic phenotype with severe liver damage

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
intrahepatic cholestasis		DOID:1852		J:215915