Establishment of Hyperbilirubinuria Rat Mutant —A New Animal Model for Jaundice—

Abstract

A new animal model for jaundice, a hyperbilirubinemic rat mutant (EHBR, Eisai hyperbilirubinuria rat), was established from Sprague-Dawley rats. Hyperbilirubinemia was inherited as an autosomal recessive trait. The gene manifesting jaundice was named“hyb”. Homozygotes developed jaundice immediately after birth, and a high bilirubin concentration was detected in plasma and urine. The plasma bilirubin levels were high in the neonatal period, but they decreased from 6 to 10 weeks old. In male homozygotes, plasma bilirubin levels increased rapidly until about 40 weeks, and decreased thereafter. Female homozygotes showed slightly high plasma bilirubin levels until 56 weeks, then increased rapidly thereafter. At 72 weeks, the plasma bilirubin level of females was comparable to that of males. About 80 percent of the plasma bilirubin was conjugated. Plasma biochemistry demonstrated the increase of total cholesterol and total bile acid in the homozygotes. Histopathologically, the homozygote was characterized by brown pigment in the hepatocytes, and glomerular lesions with mesangial expansion. From these findings it was considered that EHBR might be a useful animal model for studying constitutional conjugated hyperbilirubinemia and bilirubin metabolism.