ORIGINAL RESEARCH article
Front. Neurosci.
Sec. Neurodevelopment
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1556570
NEXMIF overexpression is associated with autism-like behaviors and alterations in dendritic arborization and spine formation in mice
Provisionally accepted
- 1Department of Biology, Boston University, Boston, United States
- 2Department of Pharmacology, Physiology & Biophysics, Chobanian & Avedisian School of Medicine, Boston University, Boston, Massachusetts, United States
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We previously found that loss of the X-linked gene NEXMIF results in ASD and intellectual disability (ID). Duplication of chromosomal segments containing NEXMIF has been associated with ASD/ID in humans, but the direct link to the NEXMIF gene, as well as the behavioral and cellular consequences of NEXMIF overexpression, have not yet been explored. Here, we report that bilateral injection of a human NEXMIF lentivirus into postnatal day 1 (P1) mouse brains results in impaired communication, short-term memory deficits, reduced social behavior, hyperactivity, repetitive/restrictive behaviors, anxiety-like behavior, and altered nociception at adolescent ages, accompanied by attenuated dendritic spine density and increased dendritic arborization. RNA sequencing revealed that elevated NEXMIF dosage leads to strong dysregulation in the expression of genes involved in synaptic transmission, neuron differentiation, and post-synaptic membrane potential. These findings indicate that NEXMIF overexpression results in transcriptional and cellular deficits that contribute to the development of ASD-like behaviors.
Keywords: Autism Spectrum Disorder, X-linked intellectual disability (XLID), overexpression, mouse behavior, NEXMIF gene, NEXMIF Duplication, Neuronal deficits
Received: 07 Jan 2025; Accepted: 23 May 2025.
Copyright: © 2025 Odamah, Nishizawa Criales and Man. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Heng-Ye Man, Department of Biology, Boston University, Boston, United States
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