A unique bilirubin-UDP-glucuronosyltransferase deficiency related to neonatal jaundice in mice.
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.
Burkhart
J G
JG
Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Armstrong
F B
FB
Eisen
E J
EJ
D000818:Animals; D005260:Female; D014453:Glucuronosyltransferase / Q000172:deficiency* / Q000235:genetics; D007565:Jaundice / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains
C019787:bilirubin glucuronoside glucuronosyltransferase; D014453:Glucuronosyltransferase