A unique bilirubin-UDP-glucuronosyltransferase deficiency related to neonatal jaundice in mice.

Abstract

This report describes biochemical and cellular characterization of a spontaneous mutation in ICR mice; the mutation has been phenotypically characterized as autosomal recessive jaundice in neonates and juveniles and given the gene symbol hub (J. Hered. 76:441-446, 1985; Mouse Newslett. 73:28, 1985). The results obtained demonstrate that (1) mice homozygous for the mutation are deficient in bilirubin-UDP-glucuronosyltransferase activity, and there is no deficiency in heterozygous mice, (2) the deficiency is lifelong, even though the clinical symptom of jaundice is transitory and restricted to neonates or juveniles, (3) bilirubin-UDP-glucuronosyltransferase activity in mutant and nonmutant mice is similarly induced by triiodothyronine, (4) glucuronidation and xylodation of bilirubin probably occur as the result of separate enzyme forms in mice, and (5) Western analysis using antibody to rat bilirubin-UDP-glucuronosyltransferase indicates that although there is no electrophoretic mobility difference, there is a diffuse band missing in mutant mice. Hepatic hyperplasia, cytomegaly, single-cell necrosis, and eosinophilic foci are also pleiotropic traits associated with homozygous but not heterozygous hub. The hub/hub mouse will be useful in the study of substrate specificity and regulation within a complex gene family and, perhaps, provide a new and useful animal model for the long-term health effects of deficiency in the metabolism of xenobiotics cleared via UDP-glucuronosyltransferase.

• Authors: J G Burkhart, F B Armstrong, E J Eisen
• Journal: Biochemical genetics (Biochem Genet) Vol. 33 Issue 9-10 Pg. 307-26 (Oct 1995) ISSN: 0006-2928 [Print] United States
• PMID: 8748456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• bilirubin glucuronoside glucuronosyltransferase
• Glucuronosyltransferase

Topics

• Animals
• Female
• Glucuronosyltransferase (deficiency, genetics)
• Jaundice (genetics, metabolism, pathology)
• Liver (metabolism, pathology)
• Male
• Mice
• Mice, Inbred ICR
• Mice, Mutant Strains