Genetic defect of bilirubin UDP-glucuronosyltransferase in the hyperbilirubinemic Gunn rat

https://doi.org/10.1016/0006-291X(91)90661-PGet rights and content

Abstract

The genetic defect of bilirubin UDP-glucuronosyltransferase (UDPGT) in the hyperbilirubinemic Gunn rat was proved to be a −1 frameshift mutation. The mutation was found not only to be located in the region where bilirubin UDPGT cDNA shared an identical sequence with 3-methylcholanthrene (3MC)-inducible UDPGT cDNA but also to occur in the same position on the two cDNAs from the mutant rat. At the 5′ end of the identical region there was a consensus sequence for splicing, of which position coincided with the boundary between the 2nd and 3rd exon of the testosterone UDPGT gene. These results strongly suggest that mRNAs for bilirubin and 3MC-inducible UDPGTs are produced from a single primary-transcript after an alternative splicing and the defects of bilirubin and 3MC-inducible UDPGTs in the mutant rat are caused by a point mutation on a common exon.

References (15)

  • H. Sato et al.

    Biochem. Biophys. Res. Commun

    (1990)
  • I.M. Arias et al.

    Am. J. Med

    (1969)
  • I. Scragg et al.

    FEBS Lett

    (1985)
  • T. Iyanagi et al.

    J. Biol. Chem

    (1989)
  • R.B. Corser et al.

    FEBS Lett

    (1987)
  • D. Harding et al.

    Biochem. Pharmacol

    (1989)
  • P.I. Mackenzie et al.

    J. Biol. Chem

    (1990)
There are more references available in the full text version of this article.

Cited by (37)

  • Preclinical Development of an AAV8-hUGT1A1 Vector for the Treatment of Crigler-Najjar Syndrome

    2019, Molecular Therapy Methods and Clinical Development
    Citation Excerpt :

    We next compared the transduction efficiency of (sc)AAV8-hUGT1A1 versus (ss)AAV8-hUGT1A1 in vitro in human hepatoma cells,19 which resulted in a similar expression of the hUGT1A1 transgene (Figure 2A). Next, in vivo comparison of the vectors was performed in a well-established model of CN syndrome, the Gunn rat.24–26 This model presents blood levels of bilirubin comparable to those observed in patients with mild symptoms and no evident signs of brain toxicity (6–12 ± mg/dL). (

  • Biochemical and molecular aspects of genetic disorders of bilirubin metabolism

    1998, Biochimica et Biophysica Acta - Molecular Basis of Disease
View all citing articles on Scopus
View full text