References
Query Results -- Details
MGI Accession ID: MGI:1313230
J Number: J:51019
Other Accession IDs:
Title: Cholesterol 7-hydroxylase knockout mouse: a model for monohydroxy bile acid-related neonatal cholestasis.
Authors: Arnon R; Yoshimura T; Reiss A; Budai K; Lefkowitch JH; Javitt NB
Journal: Gastroenterology
Volume: 115
Issue: 5
Date: 1998 Nov
Year: 1998
Pages: 1223-8
Review Status: Peer Reviewed
Abstract:
Background & Aims: Cyp 7-/- mice lack a functional cholesterol 7 alpha-hydroxylase enzyme and develop cholestasis before up-regulation of 27-hydroxycholesterol 7 alpha-hydroxylase activity. Because 7 alpha- hydroxylation is not the initial step in this metabolic pathway, we tested the hypothesis that cholesterol 7 alpha- hydroxylase is expressed at an earlier step and leads to the production of monohydroxy bile acids. Methods: Polymerase chain reaction with specific oligonucleotides was used to detect messenger RNA (mRNA) coding for cholesterol 27-hydroxylase in 5-day-old normal and Cyp 7-/- mice. Gas-liquid chromatography-mass spectrometry and reverse isotope dilution were used to identify intermediates in the cholesterol 27-hydroxylase metabolic pathway. Light and electron microscopy were used to evaluate the morphological appearance of the liver. Results: mRNA for cholesterol 27-hydroxylase was identified in the liver and spleen. The monohydroxy bile acids 3 beta-hydroxy-5-cholenoate and 27-hydpoxy-5 beta- cholanoate together with their precursor, 27- hydroxycholesterol, were identified in liver homogenates. Cholestasis, present focally, was manifested as dilated bile canaliculi, partial loss of microvilli, and retention of electron-dense biliary material. Conclusions: The cholesterol 27-hydroxylase metabolic pathway of bile acid synthesis is expressed in neonatal life. The absence of 7 alpha-hydroxylase activities unmasks the cholestatic potential of monohydroxy bile acids. The Cyp 7-/- knockout mouse mimics cholestatic events known to occur in humans and provides a unique opportunity for studying regulatory determinants.
Additional Information:
