Mice lacking two alleles of the schizophrenia risk gene Tcf4 and Olig2 display deficits in anxiety-related behavior, sensorimotor gating, and cognition.

INTRODUCTION

Oligodendrocytes (OLs) and myelination contribute to higher-order cognitive functions, and are impaired in several mental disorders, including schizophrenia (SZ). The SZ risk gene transcription factor 4 (TCF4) and OLIG2 are two critical regulators of differentiation and maturation of oligodendrocyte precursor cells (OPCs) and OLs. Tcf4-Olig2 double heterozygous deletion (Tcf4-Olig2 dHet) mice have been shown to exhibit impairments in OL differentiation and myelination.

METHODS

Therefore, we performed a comprehensive behavioral profiling using a Research Domain Criterion (RDoC)-based pipeline in this model.

RESULTS

Tcf4-Olig2 dHet mice showed impaired place learning in the positive valence system, reduced anxiety-like behaviors in the negative valence system, impaired remote fear memory in the cognitive domain, and abnormal sensorimotor gating.

DISCUSSION: Thus, subtle OLs and myelination impairments in Tcf4-Olig2 dHet mice led to several psychiatric disorder-related behavioral deficits. We conclude that Tcf4-Olig2 dHet mice represent a preclinical mouse model to study myelination-related mechanisms relevant for mental disorders.