UNLABELLED: Niemann-Pick type C (NPC) is a fatal autosomal recessive lipidosis that is characterized by lysosomal storage of cholesterol and glycosphingolipids. Patients exhibit prolonged neonatal jaundice, hepatosplenomegaly, and progressive neurodegeneration that generally result in death by the teen years. Most clinical cases are caused by mutations in the NPC1 gene. Current mouse models of NPC are not well suited for studying the liver disease due to the rapidly progressing neurological disease. To facilitate study of NPC-associated liver dysfunction, we have developed a novel mouse model using antisense oligonucleotides to ablate NPC1 expression primarily in the liver. Here, we show that the NPC1 knockdown leads to a liver disease phenotype similar to that of patients with NPC and the NPC(nih) mouse model. Key features include hepatomegaly, lipid storage, elevated serum liver enzymes, and increased apoptosis. CONCLUSION: This novel NPC1 antisense mouse model will allow delineation of the mechanism by which NPC1 dysfunction leads to liver cell death.
UNLABELLED: Niemann-Pick type C (NPC) is a fatal autosomal recessive lipidosis that is characterized by lysosomal storage of cholesterol and glycosphingolipids. Patients exhibit prolonged neonatal jaundice, hepatosplenomegaly, and progressive neurodegeneration that generally result in death by the teen years. Most clinical cases are caused by mutations in the NPC1 gene. Current mouse models of NPC are not well suited for studying the liver disease due to the rapidly progressing neurological disease. To facilitate study of NPC-associated liver dysfunction, we have developed a novel mouse model using antisense oligonucleotides to ablate NPC1 expression primarily in the liver. Here, we show that the NPC1 knockdown leads to a liver disease phenotype similar to that of patients with NPC and the NPC(nih) mouse model. Key features include hepatomegaly, lipid storage, elevated serum liver enzymes, and increased apoptosis. CONCLUSION: This novel NPC1 antisense mouse model will allow delineation of the mechanism by which NPC1 dysfunction leads to liver cell death.
Authors: William S Garver; David Jelinek; Janice N Oyarzo; James Flynn; Matthew Zuckerman; Kumar Krishnan; Byung H Chung; Randall A Heidenreich Journal: J Cell Biochem Date: 2007-05-15 Impact factor: 4.429
Authors: Eduardo P Beltroy; James A Richardson; Jay D Horton; Stephen D Turley; John M Dietschy Journal: Hepatology Date: 2005-10 Impact factor: 17.425
Authors: Y Liu; Y P Wu; R Wada; E B Neufeld; K A Mullin; A C Howard; P G Pentchev; M T Vanier; K Suzuki; R L Proia Journal: Hum Mol Genet Date: 2000-04-12 Impact factor: 6.150
Authors: S Joshua Langmade; Sarah E Gale; Andrey Frolov; Ikuko Mohri; Kinuko Suzuki; Synthia H Mellon; Steven U Walkley; Douglas F Covey; Jean E Schaffer; Daniel S Ory Journal: Proc Natl Acad Sci U S A Date: 2006-08-29 Impact factor: 11.205
Authors: Celine V M Cluzeau; Dawn E Watkins-Chow; Rao Fu; Bhavesh Borate; Nicole Yanjanin; Michelle K Dail; Cristin D Davidson; Steven U Walkley; Daniel S Ory; Christopher A Wassif; William J Pavan; Forbes D Porter Journal: Hum Mol Genet Date: 2012-05-22 Impact factor: 6.150
Authors: Charina M Ramirez; Adam M Lopez; Lam Q Le; Kenneth S Posey; Arthur G Weinberg; Stephen D Turley Journal: Biochim Biophys Acta Date: 2013-09-26
Authors: Melanie Vincent; Naomi L Sayre; Mark J Graham; Rosanne M Crooke; David J Shealy; Laura Liscum Journal: PLoS One Date: 2010-09-23 Impact factor: 3.240
Authors: Rao Fu; Christopher A Wassif; Nicole M Yanjanin; Dawn E Watkins-Chow; Laura L Baxter; Art Incao; Laura Liscum; Rohini Sidhu; Sally Firnkes; Mark Graham; Daniel S Ory; Forbes D Porter; William J Pavan Journal: Hum Mol Genet Date: 2013-05-10 Impact factor: 6.150