Niemann-Pick type C1 (Npc1) is a rare neurodegenerative disorder linked to faulty cholesterol biosynthesis and irregular lipid regulation. It's suggested that Npc1 gene suppression leads to olfactory system defects. The unsolved question lies in whether these impairments present themselves in the disease's early stages. To address this question, we examined a mouse model with the I1061T missense mutation in the Npc1 gene, reflective of human Npc1 disease. Western blotting demonstrated reduced expression of olfactory marker protein, a molecular marker of mature olfactory sensory neurons in the olfactory epithelium and bulb in Npc1 (I1061T) mice. Analysis of Tubulin beta 3 class III (Tubb3), a marker for immature and transient olfactory sensory neurons, revealed no difference between I1061T and wild-type mice, suggesting that in this animal model we could observe a decline in mature neurons in the olfactory epithelium.
Our preliminary data suggest that Npc1 mouse models are suitable for studying the olfactory system's structure. Future experiments will leverage electrophysiology to investigate whether structural deficits in the olfactory system lead to a decrease in olfactory function. This work will undoubtedly enhance our understanding of Npc1 disease progression and could possibly facilitate the use of the sense of smell as a marker to assess pharmacological treatments for the disease.