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Characterization of Dendritogenesis in Cortical Pyramidal Layer V Neurons in Niemann‐Pick Type C Disease Using Yellow Fluorescent Protein
Author(s) -
Morales Silva Roberto,
AlvaradoTorres John,
Boudewyn Lauren,
Walkley Steven
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb637
Subject(s) - niemann–pick disease, type c , yellow fluorescent protein , endosome , dendrite (mathematics) , microbiology and biotechnology , ectopic expression , chemistry , npc1 , golgi apparatus , genetically modified mouse , biology , transgene , intracellular , biochemistry , cholesterol , gene , geometry , mathematics , endoplasmic reticulum
Niemann‐Pick type C (NPC) disease is an autosomal recessive lysosomal storage disorder affecting mostly children, causing progressive neurological deterioration and death. NPC disease is caused by a mutation in either the NPC1 or NPC2 gene, leading to a loss of functional NPC1 or NPC2 protein. These proteins play a role in lipid egress from late endosomes and lysosomes, a deficiency in either results in intracellular accumulation of unesterified cholesterol and gangliosides. Storage is prominent in neurons, influencing cellular pathology, such as growth of ectopic dendrites on pyramidal neurons. This aberrant growth of dendrites following normal dendritogenesis has been documented in several lysosomal diseases characterized by ganglioside storage. Until recently, the visualization of this process depended on the Golgi method. New techniques, such as endogenous expression of fluorescent proteins, provide an in‐depth analysis of neuronal structure. We hypothesized that the accumulation of gangliosides in NPC disease will cause an initial enhancement of dendritogenesis along with ectopic dendrite growth followed by a subsequent degeneration of dendritic trees later in disease. Subsequently, we generated a transgenic Npc1 murine mouse model whose layer V cortical pyramidal neurons express yellow fluorescent protein (YFP) to investigate the dendritic abnormalities of NPC disease relative to lysosomal storage. Confocal imaging and Neurolucida Software are being used to image YFP+ pyramidal neurons, which will be analyzed for changes in dendritic size, complexity and pathological state.