Hereditary chronic conjugated hyperbilirubinemia in mutant rats caused by defective hepatic anion transport

Hepatology. 1985 Jul-Aug;5(4):573-9. doi: 10.1002/hep.1840050408.

Abstract

A mutant rat strain is described with autosomal recessive conjugated hyperbilirubinemia. Transport of conjugated bilirubin and tetrabromosulfophthalein from liver to bile is severely impaired whereas uptake of organic anions from plasma to liver is normal. During the first 10 days of life, serum bilirubin levels are 147 +/- 11 mumoles per liter with 68.7% diconjugates and 27.9% monoconjugates. In adult rats, serum bilirubin is 33 +/- 8 mumoles per liter with 81.8% diconjugates and 12.1% monoconjugates vs. 0.3 +/- 0.1 mumole per liter unconjugated bilirubin in normal adult rats. Bile acid metabolism is only mildly affected. In young rats, serum bile acid levels are normal. In adult rats, bile acid levels are elevated to 49 +/- 11 mumoles per liter vs. 10 +/- 6 mumoles per liter in normal rats. The bile flow in mutant rats is reduced to about 50%. This might be caused by a reduction of the bile acid-independent bile fraction. Liver marker enzyme activities in mutant rat serum are normal. Liver morphology is also normal. Total urinary coproporphyrin excretion is not elevated but urinary coproporphyrin isomer I excretion is increased, a pattern like that in Dubin-Johnson syndrome in humans. However, unlike Dubin-Johnson syndrome, the mutant rats do not have the characteristic black hepatic pigment. These rats provide a unique model to study mechanisms of bile formation and cholestasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile / metabolism*
  • Bile Acids and Salts / metabolism
  • Bilirubin / metabolism
  • Biological Transport
  • Coproporphyrins / urine
  • Female
  • Genes, Recessive
  • Hyperbilirubinemia, Hereditary / genetics
  • Hyperbilirubinemia, Hereditary / metabolism*
  • Liver / metabolism*
  • Male
  • Rats
  • Rats, Mutant Strains / metabolism*
  • Sulfobromophthalein

Substances

  • Bile Acids and Salts
  • Coproporphyrins
  • Sulfobromophthalein
  • Bilirubin