| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-83 |
Sentence |
denotes |
Disruption of the ugt1 locus in mice resembles human Crigler-Najjar type I disease. |
| T2 |
84-328 |
Sentence |
denotes |
The 9 UDP-glucuronosyltranferases (UGTs) encoded by the UGT1 locus in humans are key enzymes in the metabolism of most drugs as well as endogenous substances such as bile acids, fatty acids, steroids, hormones, neurotransmitters, and bilirubin. |
| T3 |
329-484 |
Sentence |
denotes |
Severe unconjugated hyperbilirubinemia in humans that suffer from Crigler-Najjar type I disease results from lesions in the UGT1A1 gene and is often fatal. |
| T4 |
485-639 |
Sentence |
denotes |
To examine the physiological importance of the Ugt1 locus in mice, this locus was rendered non-functional by interrupting exon 4 to create Ugt1(-/-) mice. |
| T5 |
640-869 |
Sentence |
denotes |
Because UGT1A1 in humans is responsible for 100% of the conjugated bilirubin, it followed that newborn Ugt1(-/-) mice developed serum levels of unconjugated bilirubin that were 40-60 times higher than Ugt1(+/-) or wild-type mice. |
| T6 |
870-1088 |
Sentence |
denotes |
The result of extreme unconjugated bilirubin in Ugt1(-/-) mice, comparable to the induced levels noted in patients with Crigler-Najjar type 1 disease, is fatal in neonatal Ugt1(-/-) mice within 2 weeks following birth. |
| T7 |
1089-1160 |
Sentence |
denotes |
The extreme jaundice is present as a phenotype in skin color after 8 h. |
| T8 |
1161-1305 |
Sentence |
denotes |
Neonatal Ugt1(-/-) mice exhibit no detectable UGT1A-specific RNA, which corresponds to a complete absence of UGT1A proteins in liver microsomes. |
| T9 |
1306-1466 |
Sentence |
denotes |
Conserved glucuronidation activity attributed to the Ugt1 locus can be defined in Ugt1(-/-) mice, because UGT2-dependent glucuronidation activity is unaffected. |
| T10 |
1467-1629 |
Sentence |
denotes |
Remarkably, the loss of UGT1A functionality in liver results in significant alterations in cellular metabolism as investigated through changes in gene expression. |
| T11 |
1630-1855 |
Sentence |
denotes |
Thus, the loss of UGT1A function in Ugt1(-/-) mice leads to a metabolic syndrome that can serve as a model to further investigate the toxicities associated with unconjugated bilirubin and the impact of this disease in humans. |
