抄録
In this report we describe our recent histological and biochemical studies to characterize the pathogenic mechanisms of cerebellar hypoplasia exhibited by homozygous Sprague-Dawley-strain Gunn rats and gene mapping of bilirubin UDP-glucuronosyltransferase (BRGT) .
Gunn rats are a mutant strain with autosomal recessive trait of hyperbilirubinemia. Homozygous Sprague-Dawley-strain Gunn rats shows marked hyperbilirubinemia and the cerebellar development of the rats is damaged. The severely damaged parts in the cerebellum are known to be anterior and middle lobes while posterior (lobules IXc, IXd and X) are less affected. The most effective day of bilirubin on the cerebellar development is centered on postnatal day 7. It is suggested that the preferential deposition of bilirubin in Purkinje cells of anterior and middle lobes may occur in jaundiced Gunn rat infants, by which the cells are damaged eventually leading to degeneration. The genetic defect in Gunn rats is reported to be deficient in both hepatic BRGT and 3-methylcholanthrene-inducible 4-nitrophenol UDP-glucuronosyltransferase (4-NP-GT) . Both BRGT and 4-NPGT are located on the same chromosome. Sato et al. (1990) isolated a 1763-bp cDNA for rat liver BRGT. The BRGT activity detected by autoradiography on a thin layer chromatogram by transfection of the vector carrying the cDNA into COST cells. The cDNA shares an identical 913-bp sequence with that for rat liver 4-NPGT. A-1 frameshift was found in the locus of 4-NPGT of jaundiced Gunn rats. The result suggests that the multiple defects of UDP-glucuronosyltransferase isoenzymes observed in the Gunn rats may be produced by a single-mutated-locus after an alternative splicing of the identical 913-bp region.
