Genetic background modifies phenotypic severity and longevity in a mouse model of Niemann-Pick disease type C1.

ABSTRACT: Niemann-Pick disease type C1 (NPC1) is a rare, fatal neurodegenerative disorder characterized by lysosomal accumulation of unesterified cholesterol and glycosphingolipids. These subcellular pathologies lead to phenotypes of hepatosplenomegaly, neurological degeneration and premature death. NPC1 is extremely heterogeneous in the timing of clinical presentation and is associated with a wide spectrum of causative NPC1 mutations. To study the genetic architecture of NPC1, we have generated a new NPC1 mouse model, Npc1^em1PavNpc1^{em1Pav/em1Pav} mutants showed notably reduced NPC1 protein compared to controls and displayed the pathological and biochemical hallmarks of NPC1. Interestingly, Npc1^{em1Pav/em1Pav} mutants on a C57BL/6J genetic ba

SUBMITTER: Rodriguez-Gil JL 

PROVIDER: S-EPMC7075069 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature