Abstract
Niemann-Pick C disease is a neurovisceral disorder caused by mutations in the NPC gene that result in systemic accumulation of intracellular cholesterol. Although neurodegeneration defines the disease's severity, in most patients it is preceded by hepatic complications such as cholestatic jaundice or hepatomegaly. To analyze the contribution of the hepatic disease in Niemann-Pick C disease progression and to evaluate the degree of primary and secondary hepatic damage, we generated a transgenic mouse with liver-selective expression of NPC1 from embryonic stages. Hepatic NPC1 re-expression did not ameliorate the onset and progression of neurodegeneration of the NPC1-null animal. However, the mice showed reduced hepatomegalia and dramatic, although not complete, reduction of hepatic cholesterol and serum bile salts, bilirubin, and transaminase levels. Therefore, hepatic primary and secondary cholesterol deposition and damage occur simultaneously during Niemann-Pick C disease progression.
References
Nov 14, 1997·Nature Genetics·P MarkelK J Moore
Mar 21, 2000·Genesis : the Journal of Genetics and Development·C KellendonkF Tronche
Nov 15, 2000·Genome Research·J L HartleyM A Brasch
Feb 22, 2002·Genesis : the Journal of Genetics and Development·Fereshteh ParvizStephen A Duncan
Nov 6, 2002·Human Molecular Genetics·Stacie K LoftusWilliam J Pavan
Jan 16, 2003·The Journal of Comparative Neurology·Justyna R SarnaRichard Hawkes
Mar 30, 2004·Genesis : the Journal of Genetics and Development·Giuseppe TestaA Francis Stewart
Nov 9, 2004·Developmental Biology·Katherine Krupczak-HollisRobert H Costa
Sep 12, 2009·Journal of Lipid Research·William S GarverGordon A Francis
Dec 17, 2009·Human Molecular Genetics·Matthew J ElrickAndrew P Lieberman
Jun 8, 2010·Orphanet Journal of Rare Diseases·Marie T Vanier
Mar 25, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Manuel E LopezMatthew P Scott
May 18, 2011·Journal of Lipid Research·Tyler SchwendSara C Ahlgren
Jun 17, 2011·Nature·William C SkarnesAllan Bradley
Aug 13, 2011·Human Molecular Genetics·Albert GiraltEsther Pérez-Navarro
Aug 23, 2011·Human Molecular Genetics·Ting YuAndrew P Lieberman
Apr 13, 2012·Journal of Alzheimer's Disease : JAD·Ivan BorbonRobert P Erickson
Jan 8, 2013·Journal of Applied Genetics·Robert P Erickson
Aug 3, 2013·Disease Models & Mechanisms·Manuel E Lopez, Matthew P Scott
Oct 19, 2013·Orphanet Journal of Rare Diseases·Eugen MengelStefan A Kolb
Mar 19, 2015·International Journal of Pediatrics·Hanna Alobaidy
Citations
Jan 13, 2018·Endocrine Reviews·Amel LamriDavid Meyre
Dec 2, 2020·International Journal of Molecular Sciences·Valentina Pallottini, Frank W Pfrieger
Dec 22, 2020·The American Journal of Pathology·Elsa Meneses-SalasCarles Rentero
Nov 4, 2020·Scientific Reports·Andreea ChioreanDavid Meyre