A UNIQUE BILIRUBIN-UDP-GLUCURONOSYLTRANSFERASE DEFICIENCY RELATED TO NEONATAL JAUNDICE IN MICE

This report describes biochemical and cellular characterization of a s pontaneous mutation in ICR mice; the mutation has been phenotypically characterized as autosomal recessive jaundice in neonates and juvenile s and given the gene symbol hub (J. Hered. 76:441-446, 1985; Mouse New slett. 73:28, 1985). The results obtained demonstrate that (1) mice ho mozygous for the mutation are deficient in bilirubin-UDP-glucuronosylt ransferase activity, and there is no deficiency in heterozygous mice, (2) the deficiency is lifelong, even though the clinical symptom of ja undice is transitory and restricted to neonates or juveniles, (3) bili rubin-UDP-glucuronosyltransferase activity in mutant and nonmutant mic e is similarly induced by triiodothyronine, (4) glucuronidation and xy lodation of bilirubin probably occur as the result of separate enzyme forms in mice, and (5) Western analysis using antibody to rat bilirubi n-UDP-glucuronosyltransferase indicates that although there is no elec trophoretic mobility difference, there is a diffuse band missing in mu tant mice. Hepatic hyperplasia, cytomegaly, single-cell necrosis, and eosinophilic foci are also pleiotropic traits associated with homozygo us but not heterozygous hub. The hub/hub mouse will be useful in the s tudy of substrate specificity and regulation within a complex gene fam ily and, perhaps, provide a new and useful animal model for the long-t erm health effects of deficiency in the metabolism of xenobiotics clea red via UDP-glucuronosyltransferase.