Universidad de Murcia. Departamento de Biología Celular e Histología
Abstract
Niemann–Pick type C1 (NPC1) disease is a
lysosomal storage disorder caused by mutation of Npc1
or Npc2 gene, resulting in various progressive
pathological features. Myelin defection is a major
pathological problem in Npc1 mutant mice; however,
impairment of myelin proteins in the developing brain is
still incompletely understood. In this study, we showed
that the expression of myelin genes and proteins is
strongly inhibited from postnatal day 35 onwards
including reduced myelin basic protein (MBP)
expression in the brain. Furthermore, myelination
characterized by MBP immunohistochemistry was
strongly perturbed in the forebrain, moderately in the
midbrain and cerebellum, and slightly in the hindbrain.
Our results demonstrate that mutation of the Npc1 gene
is sufficient to cause severe and progressive defects in
myelination in the mouse brain