Role of Na(v)1.6 and Visual Experience in Retinal and Brain Maturation during the Early Postnatal Period

Abstract

The Scn8a gene encodes the voltage-gated sodium channel isoform Nav1.6, playing a key role in saltatory conduction across the nodes of Ranvier in the CNS. One Scn8a mutation, termed degenerating muscle (dmu) (Scn8admu/dmu) results in premature protein synthesis, causing reduced retinal function, hindlimb paralysis and premature death, suggesting possible disruptions to overall cellular integrity and functions. In my dissertation, I sought to understand how the Scn8admu mutation asserts its pathology. Disparity in gene expression patterns were identified between mutants and wildtype animals through qRT-PCR analysis of 11 genes. Results suggested a trend towards downregulation of genes involved with intracellular transport in mutants. Next, I examined the state of the intracellular scaffold within the neurons of mutant animals by staining for neurofilaments. The neurofilamentous network of mutant retina and cerebella are in a state of disarray. This disruption may be the root cause of observed phenotypes manifested by mutant animals.