Subject Area
Biology
Description
Hayden Lens ’23, Major: Biology
Mary Boghos ’23, Major: Biology
Faculty Mentor: Dr. Ileana Soto Reyes, Biology
The Npc1nmf164 mutant mouse is an animal model for the human disease Niemann-Pick type C (NPC). NPC is a lysosomal storage disease that is acquired by autosomal recessive inheritance. It is mostly caused by mutations in NPC1, a protein that transports cholesterol out of the lysosomes, therefore abnormal accumulation of cholesterol in lysosomes is a hallmark of NPC. Cerebellar Purkinje cells (PCs) are severely affected by NPC, in fact, PCs degenerate first and to a larger extent at childhood stages. Therefore, we have been studying how the Npc1nmf164 mutation affects PC development during cerebellar postnatal development, a stage that precedes the degeneration of these cells in NPC.
For the purpose of these experiments, Npc1nmf164 mice are used to examine changes in PCs using histological methods, microscopy, and imaging analysis. Our results suggest that a lack of NPC1 alters the development of dendrites and synapses in PC by altering metabolic pathways. It has been shown that a lack of lysosomal NPC1 causes the hyperactivation of the anabolic mTORC1 pathway, which also inhibits the production of lysosomes and catabolic processes such as autophagy. This disruption of metabolic pathways during the development of PCs may lead to developmental defects and a predisposition to degeneration.
Publisher
Providence College
Date
4-27-2023
Type
Poster
Format
Text
Language
English
