Lack of Annexin A6 Exacerbates Liver Dysfunction and Reduces Lifespan of Niemann-Pick Type C Protein–Deficient Mice

Abstract Niemann-Pick type C disease (NP-C) is a lysosomal storage disorder characterized by cholesterol accumulation caused loss-of-function mutations in the Npc1 gene. NP-C primarily affects brain, causing neuronal damage and affecting motor coordination. In addition, considerable liver malfunction common. Recently, we demonstrated that depletion of annexin A6 (ANXA6), which most abundant involved transport, ameliorated mutant cells. To evaluate potential contribution ANXA6 progression disease, double-knockout mice (Npc1-/-/Anxa6-/-) were generated examined for lifespan, neurological hepatic functions, as well histology ultrastructure. Strikingly, lack NPC1-deficient animals did not prevent cerebellar degeneration phenotype but further deteriorated their compromised functions reduced lifespan. Moreover, livers Npc1-/-/Anxa6-/- contained significantly elevated number foam cells congesting sinusoidal space, feature commonly associated with inflammation. We hypothesize deficiency Npc1-/- do reverse dysfunction it worsens overall function, exacerbating failure disease.