Convergence of independent DISC1 mutations on impaired neurite growth via decreased UNC5D expression.

ABSTRACT: The identification of convergent phenotypes in different models of psychiatric illness highlights robust phenotypes that are more likely to be implicated in disease pathophysiology. Here, we utilize human iPSCs harboring distinct mutations in DISC1 that have been found in families with major mental illness. One mutation was engineered to mimic the consequences on DISC1 protein of a balanced translocation linked to mental illness in a Scottish pedigree; the other mutation was identified in an American pedigree with a high incidence of mental illness. Directed differentiation of these iPSCs using NGN2 expression shows rapid conversion to a homogenous population of mature excitatory neurons. Both DISC1 mutations result in reduced DISC1 protein expression, and show subtle effects on certain pr

SUBMITTER: Srikanth P 

PROVIDER: S-EPMC6224395 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature