DPYSL2/CRMP2 isoform B knockout in human iPSC-derived glutamatergic neurons confirms its role in mTOR signaling and neurodevelopmental disorders.

ABSTRACT: The DPYSL2/CRMP2 gene encodes a microtubule-stabilizing protein crucial for neurogenesis and is associated with numerous psychiatric and neurodegenerative disorders including schizophrenia, bipolar disorder, and Alzheimer's disease. DPYSL2 generates multiple RNA and protein isoforms, but few studies have differentiated between them. We previously reported an association of a functional variant in the DPYSL2-B isoform with schizophrenia (SCZ) and demonstrated in HEK293 cells that this variant reduced the length of cellular projections and created transcriptomic changes that captured schizophrenia etiology by disrupting mTOR signaling-mediated regulation. In the present study, we follow up on these results by creating, to our knowledge, the first models of endogenous DPYSL2-B knockout in hum

SUBMITTER: Feuer KL 

PROVIDER: S-EPMC11138811 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature