Loss-of-function mutation in Mirta22/Emc10 rescues specific schizophrenia-related phenotypes in a mouse model of the 22q11.2 deletion.

ABSTRACT: Identification of protective loss-of-function (LoF) mutations holds great promise for devising novel therapeutic interventions, although it faces challenges due to the scarcity of protective LoF alleles in the human genome. Exploiting the detailed mechanistic characterization of animal models of validated disease mutations offers an alternative. Here, we provide insights into protective-variant biology based on our characterization of a model of the 22q11.2 deletion, a strong genetic risk factor for schizophrenia (SCZ). Postnatal brain up-regulation of Mirta22/Emc10, an inhibitor of neuronal maturation, represents the major transcriptional effect of the 22q11.2-associated microRNA dysregulation. Here, we demonstrate that mice in which the Df(16)A deficiency is combined with a

SUBMITTER: Diamantopoulou A 

PROVIDER: S-EPMC5544257 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature