Phenotypes Associated with This Genotype

Genotype
MGI:5618808

• Allelic Composition: Atp8b1^tm1Nbf/Atp8b1^tm1Nbf; Por^tm1Wolf/Por^tm1Wolf; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:215915 )

• mice fed a 0.03% cholic acid-supplemented diet directly from weaning die within a week after the start of the diet

• however, mice fed a 0.03% cholic acid-supplemented diet starting at 4 weeks of age for 4 weeks survive

growth/size/body

weight loss ( J:215915 )

• mice fail to gain weight and even lose weight after starting of 0.03% cholic acid-supplemented diet at 4 weeks of age

increased liver weight ( J:215915 )

• liver weights are increased in mice fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age

• mice fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age do not exhibit fibrosis in the liver

homeostasis/metabolism

increased circulating bilirubin level ( J:215915 )

• after 4 weeks of cholic acid-supplemented diet started at 4 weeks of age, mice exhibit enhanced plasma bilirubin levels

increased circulating alanine transaminase level ( J:215915 )

• after 4 weeks of cholic acid-supplemented diet started at 4 weeks of age, mice exhibit a mild elevation in plasma alanine transaminase levels

increased circulating alkaline phosphatase level ( J:215915 )

• after 4 weeks of cholic acid-supplemented diet started at 4 weeks of age, mice exhibit a mild elevation in plasma alkaline phosphatase levels

abnormal bile salt homeostasis ( J:215915 )

• after 4 weeks on a cholic acid-supplemented diet, plasma bile salts predominantly consist of about 90% taurocholate (TC) and about 7% tauro-beta-muricholate (TbetaMC) and a low concentration of about 0.4% of the secondary bile salt taurochenodeoxycholate (TDC) is seen compared to about 70% TC and 20% TbetaMC in single Atp8b1 homozygotes

• after 4 weeks on a cholic acid-supplemented diet, biliary bile salts predominantly consist of about 90% TC and about 9% TbetaMC compared to 55% TC and 40% TbetaMC in single Atp8b1 homozygotes

• after 4 weeks on a cholic acid-supplemented diet, bile salt hydrophobicity index of plasma is elevated but the hydrophobicity index of bile is unaltered, indicating that the plasma bile salt pool is more hydrophobic

increased bile salt level ( J:215915 )

• after 4 weeks of cholic acid-supplemented diet started at 4 weeks of age, mice exhibit a strong elevation in plasma bile salt levels

liver/biliary system

bile duct proliferation ( J:215915 )

• mice fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age, exhibit a slight increase in bile duct proliferation

increased liver weight ( J:215915 )

• liver weights are increased in mice fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age

• mice fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age do not exhibit fibrosis in the liver

abnormal bile secretion ( J:215915 )

• after 4 weeks of cholic acid-supplemented diet started at 4 weeks of age, bile flow is strongly (about 3-fold) reduced

• mice, however show normal bile salt output when fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age

cholestasis ( J:215915 )

• mice fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age develop a severe cholestatic phenotype with mild liver damage

endocrine/exocrine glands

bile duct proliferation ( J:215915 )

• mice fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age, exhibit a slight increase in bile duct proliferation

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