Year: 2019
Type: dissertation
Abstract: Misregulation of nSR100 and its target microexons are common in a large proportion of ASD patients and cause ASD-associated features in mice. This thesis explores nSR100 and its target splicing program as a potential therapeutic target using a conditional knockout allele, nSR100GT. I show that nSR100 protein is effectively depleted in the cortical regions of nSR100GT mutant mice at E17.5, E18.5, and P2 stages, which correlates with phenotypes overlapping with all core behavioral domains of ASD. I show that tamoxifen-mediated rescue in prenatal nSR100GT animals restores nSR100 protein and microexon inclusion levels comparable to those observed in wildtype mice. Collectively my thesis research shows that the nSR100GT mouse strain holds the promise for examining phenotypic effects of nSR100 reactivation in ASD-like mice at different developmental stages, and complimentary models are also to be considered for investigating the therapeutic potential of targeting nSR100 in the context of ASD.
Source: TSpace (University of Toronto)
Author: Juli Wang
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3135772179