Neurons Generated by Direct Conversion of Fibroblasts Reproduce Synaptic Phenotype Caused by Autism-associated Neuroligin-3 Mutation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2013 Sep 19

PMID 24046374

Citations 46

Authors

Soham Chanda

Samuele Marro

Marius Wernig

Thomas C Sudhof

Affiliations

Soon will be listed here.

Abstract

Recent studies suggest that induced neuronal (iN) cells that are directly transdifferentiated from nonneuronal cells provide a powerful opportunity to examine neuropsychiatric diseases. However, the validity of using this approach to examine disease-specific changes has not been demonstrated. Here, we analyze the phenotypes of iN cells that were derived from murine embryonic fibroblasts cultured from littermate wild-type and mutant mice carrying the autism-associated R704C substitution in neuroligin-3. We show that neuroligin-3 R704C-mutant iN cells exhibit a large and selective decrease in AMPA-type glutamate receptor-mediated synaptic transmission without changes in NMDA-type glutamate receptor- or in GABAA receptor-mediated synaptic transmission. Thus, the synaptic phenotype observed in R704C-mutant iN cells replicates the previously observed phenotype of R704C-mutant neurons. Our data show that the effect of the R704C mutation is applicable even to neurons transdifferentiated from fibroblasts and constitute a proof-of-concept demonstration that iN cells can be used for cellular disease modeling.

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