Congenital Jaundice in Rats, Due to a Defect in Glucuronide Formation1

Abstract

It has recently been reported that bilirubin is excreted in the bile as a water-soluble glucuronide (1-3). The conjugation of bilirubin is believed to occur mainly in the liver (4, 5). In vitro, forma-tion of bilirubin glucuronide has been demon-strated with a system containing liver microsomes as the enzyme source and uridine diphosphate glu-curonic acid as the glucuronic acid donor (5, 6). Since conjugation of bilirubin appears to be es-sential for its excretion in the bile, a defect in the glucuronide forming mechanism would result in impaired pigment excretion and, hence, in reten-tion of free bilirubin in the blood. In preliminary communications (7, 8), such de-fects in glucuronide formation have been reported in congenital nonhemolytic nonobstructive jaun-dice in man (9) and in hereditary nonhemolytic jaundice in rats (10). The present report is con-cerned with the details of the murine studies, while the human syndrome will be considered in a sepa-rate communication. MATERIALS AND METHODS Nonjaundiced Wistar rats, known to be carriers of the jaundice trait, were donated by Dr. W. E. Castle at the University of California in Berkeley. Litters obtained by mating pairs of these animals 3 regularly included one or more offspring with jaundice. Nonjaundiced litter mates and normal Wistar and Sprague-Dawley rats served as controls. Only male animals of at least 200 Gm. body weight were used for the experiments. The rats were housed in specially built glass cages which