NEXMIF overexpression is associated with autism-like behaviors and alterations in dendritic arborization and spine formation in mice
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 N...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-06-01
|
| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2025.1556570/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850218689982365696 |
|---|---|
| author | KathrynAnn Odamah Mauricio Toyoki Nishizawa Criales Heng-Ye Man Heng-Ye Man Heng-Ye Man |
| author_facet | KathrynAnn Odamah Mauricio Toyoki Nishizawa Criales Heng-Ye Man Heng-Ye Man Heng-Ye Man |
| author_sort | KathrynAnn Odamah |
| collection | DOAJ |
| description | 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 developed a lentivirus containing the human NEXMIF gene which was bilaterally injected into the ventricles of newborn mice. At adolescent ages, the mice were subjected to various behavioral assays to assess the presence of ASD-like behaviors and comorbidities, followed by the collection of brain tissue to examine changes in neuron morphology, protein expression, and the transcriptome. We report that NEXMIF overexpression in mice led to 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. 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. Moreover, cultured neurons overexpressing NEXMIF displayed increased dendritic arborization. These findings indicate that NEXMIF overexpression results in transcriptional and cellular deficits that contribute to the development of ASD-like behaviors. |
| format | Article |
| id | doaj-art-b21cf2b576e14084bc8168534816b685 |
| institution | OA Journals |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj-art-b21cf2b576e14084bc8168534816b6852025-08-20T02:07:38ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-06-011910.3389/fnins.2025.15565701556570NEXMIF overexpression is associated with autism-like behaviors and alterations in dendritic arborization and spine formation in miceKathrynAnn Odamah0Mauricio Toyoki Nishizawa Criales1Heng-Ye Man2Heng-Ye Man3Heng-Ye Man4Department of Biology, Boston University, Boston, MA, United StatesDepartment of Biology, Boston University, Boston, MA, United StatesDepartment of Biology, Boston University, Boston, MA, United StatesDepartment of Pharmacology, Physiology & Biophysics, Boston University School of Medicine, Boston, MA, United StatesCenter for Systems Neuroscience, Boston University, Boston, MA, United StatesWe 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 developed a lentivirus containing the human NEXMIF gene which was bilaterally injected into the ventricles of newborn mice. At adolescent ages, the mice were subjected to various behavioral assays to assess the presence of ASD-like behaviors and comorbidities, followed by the collection of brain tissue to examine changes in neuron morphology, protein expression, and the transcriptome. We report that NEXMIF overexpression in mice led to 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. 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. Moreover, cultured neurons overexpressing NEXMIF displayed increased dendritic arborization. These findings indicate that NEXMIF overexpression results in transcriptional and cellular deficits that contribute to the development of ASD-like behaviors.https://www.frontiersin.org/articles/10.3389/fnins.2025.1556570/fullAutism Spectrum disorderX-linked intellectual disability (XLID)overexpressionmouse behaviorNEXMIF geneNEXMIF duplication |
| spellingShingle | KathrynAnn Odamah Mauricio Toyoki Nishizawa Criales Heng-Ye Man Heng-Ye Man Heng-Ye Man NEXMIF overexpression is associated with autism-like behaviors and alterations in dendritic arborization and spine formation in mice Frontiers in Neuroscience Autism Spectrum disorder X-linked intellectual disability (XLID) overexpression mouse behavior NEXMIF gene NEXMIF duplication |
| title | NEXMIF overexpression is associated with autism-like behaviors and alterations in dendritic arborization and spine formation in mice |
| title_full | NEXMIF overexpression is associated with autism-like behaviors and alterations in dendritic arborization and spine formation in mice |
| title_fullStr | NEXMIF overexpression is associated with autism-like behaviors and alterations in dendritic arborization and spine formation in mice |
| title_full_unstemmed | NEXMIF overexpression is associated with autism-like behaviors and alterations in dendritic arborization and spine formation in mice |
| title_short | NEXMIF overexpression is associated with autism-like behaviors and alterations in dendritic arborization and spine formation in mice |
| title_sort | nexmif overexpression is associated with autism like behaviors and alterations in dendritic arborization and spine formation in mice |
| topic | Autism Spectrum disorder X-linked intellectual disability (XLID) overexpression mouse behavior NEXMIF gene NEXMIF duplication |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2025.1556570/full |
| work_keys_str_mv | AT kathrynannodamah nexmifoverexpressionisassociatedwithautismlikebehaviorsandalterationsindendriticarborizationandspineformationinmice AT mauriciotoyokinishizawacriales nexmifoverexpressionisassociatedwithautismlikebehaviorsandalterationsindendriticarborizationandspineformationinmice AT hengyeman nexmifoverexpressionisassociatedwithautismlikebehaviorsandalterationsindendriticarborizationandspineformationinmice AT hengyeman nexmifoverexpressionisassociatedwithautismlikebehaviorsandalterationsindendriticarborizationandspineformationinmice AT hengyeman nexmifoverexpressionisassociatedwithautismlikebehaviorsandalterationsindendriticarborizationandspineformationinmice |