A new mutant strain of rats with hereditary acholuric jaundice, now known as "Gunn rat", was discovered in 1934 by C.K. Gunn in the breeding stock of Wistar rats at the Connaught Laboratories, Toronto, Canada. The jaundiced condition has been characterized as an autosomal recessive inheritance, and the homozygote (jj) of Gunn rats is evidenced to be defective or extremely low in hepatic bilirubin UDP-glucuronyltransferase activity resulting in unconjugated hyperbilirubinemia and hence often kernicterus. From these points of view the Gunn strain of rats is generally regarded as an animal model comparable to a human inborn error of bilirubin metabolism, Crigler-Najjar syndrome, Type I, which is frequently accompanied by kernicterus in the neonatal period with rare exceptions. Hyperbilirubinemic Gunn rats have been used not only for biochemical and morphological investigations on pathogenic mechanisms of kernicterus including neurotoxicity of bilirubin in the central nervous system, but also for studies on the photochemical modification of bilirubin, the formation, transport, conjugation and excretion systems of the pigment in the liver and other tissues, mechanisms of renal urinary concentration insufficiency (polyuria) and cerebellar hypoplasia, behavioral disturbances and so forth. In this report we review advances in chemistry and metabolism of bilirubin, and biochemical, morphological and behavioral observations on the characteristic features of hyperbilirubinemic Gunn rats.
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