Developmental loss of MeCP2 from VIP interneurons impairs cortical function and behavior.

Mossner, James M; Batista-Brito, Renata; Pant, Rima; Cardin, Jessica A · Elife · 2020

basic_science · Level V

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Abstract

Rett Syndrome is a devastating neurodevelopmental disorder resulting from mutations in the gene <i>MECP2</i>. Mutations of <i>Mecp2</i> that are restricted to GABAergic cell types largely replicate the behavioral phenotypes associated with mouse models of Rett Syndrome, suggesting a pathophysiological role for inhibitory interneurons. Recent work has suggested that vasoactive intestinal peptide-expressing (VIP) interneurons may play a critical role in the proper development and function of cortical circuits, making them a potential key point of vulnerability in neurodevelopmental disorders. However, little is known about the role of VIP interneurons in Rett Syndrome. Here we find that loss of MeCP2 specifically from VIP interneurons replicates key neural and behavioral phenotypes observed following global <i>Mecp2</i> loss of function.

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