Regional and developmental expression of the Npc1 mRNA in the mouse brain

Niemann-Pick type C (NP-C) disease is a fatal, autosomal recessive disorder of cholesterol metabolism that results in progressive central nervous syst em deterioration and premature death. Recently, a gene mutated in NP-C dise ase (NPC1) was identified in both human patients and in the npc(nih) mouse model. Although the function of the NPC1 gene is at present unknown, determ ining the pattern of its expression in the brain may facilitate identificat ion of the mechanisms underlying the neuropathology of this disease and in identifying relevant targets for any potential therapeutic intervention. We have used in situ hybridization techniques to characterize the pattern of Npc1 mRNA expression in both the wildtype and the npc(nih) mutant mouse bra in. In adult animals of both genotypes, the Npc1 mRNA was detected in the m ajority of neurons in nearly all regions, but at significantly higher level s in the cerebellum and in specific pontine nuclei. Analysis of Npc1 mRNA l evels during development in the wild-type mouse indicated that this transcr ipt was expressed in neurons as early as embryonic day 15 and that a signif icant region-specific pattern of expression was established by postnatal da y 7. Our data suggest that whereas the NPC1 gene is widely expressed in neu rons of the brain, the higher levels of expression in the cerebellum and po ntine structures established by early postnatal ages may make these regions more susceptible to neuronal dysfunction in NP-C disease.