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Significance A major challenge in modeling human diseases is to replicate disease phenotypes in neurons that are differentiated from nonneuronal cells, such as pluripotent stem cells or fibroblasts. However, evidence that phenotypes observed with this approach replicate an endogenous disease phenotype is lacking. This study demonstrates that induced neuronal (iN) cells obtained by direct conversion of fibroblasts to neurons, when produced from a previously described mouse mutant in neuroligin-3 that is linked to autism, exhibited a phenotype similar to that observed in endogenous neurons. These data show that the mutation studied is highly penetrant phenotypically and also that iN cells can faithfully reproduce a phenotype observed in endogenous neurons, thus validating the use of iN cells for studying disease models.

Neurons generated by direct conversion of fibroblasts reproduce synaptic phenotype caused by autism-associated neuroligin-3 mutation