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Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism

Immune dysregulation has been noted consistently in individuals with autism spectrum disorder (ASD) and their families, including the presence of autoantibodies reactive to fetal brain proteins in nearly a quarter of mothers of children with ASD versus less than 1% in mothers of typically developing...

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Autores principales: Jones, Karen L., Pride, Michael C., Edmiston, Elizabeth, Yang, Mu, Silverman, Jill L., Crawley, Jacqueline N., Van de Water, Judy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310680/
https://www.ncbi.nlm.nih.gov/pubmed/29955164
http://dx.doi.org/10.1038/s41380-018-0126-1
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author Jones, Karen L.
Pride, Michael C.
Edmiston, Elizabeth
Yang, Mu
Silverman, Jill L.
Crawley, Jacqueline N.
Van de Water, Judy
author_facet Jones, Karen L.
Pride, Michael C.
Edmiston, Elizabeth
Yang, Mu
Silverman, Jill L.
Crawley, Jacqueline N.
Van de Water, Judy
author_sort Jones, Karen L.
collection PubMed
description Immune dysregulation has been noted consistently in individuals with autism spectrum disorder (ASD) and their families, including the presence of autoantibodies reactive to fetal brain proteins in nearly a quarter of mothers of children with ASD versus less than 1% in mothers of typically developing children. Our lab recently identified the peptide epitope sequences on seven antigenic proteins targeted by these maternal autoantibodies. Through immunization with these peptide epitopes, we have successfully created an endogenous, antigen-driven mouse model that ensures a constant exposure to the salient autoantibodies throughout gestation in C57BL/6J mice. This exposure more naturally mimics what is observed in mothers of children with ASD. Male and female offspring were tested using a comprehensive sequence of behavioral assays as well as measures of health and development highly relevant to ASD. We found that MAR-ASD male and female offspring had significant alterations in development and social interactions during dyadic play. Although 3-chambered social approach was not significantly different, fewer social interactions with an estrous female were noted in the adult male MAR-ASD animals, as well as reduced vocalizations emitted in response to social cues with robust repetitive self-grooming behaviors relative to saline treated controls. The generation of MAR ASD-specific epitope autoantibodies in female mice prior to breeding created a model that demonstrates for the first time that ASD-specific antigen-induced maternal autoantibodies produced alterations in a constellation of ASD-relevant behaviors.
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spelling pubmed-63106802018-12-28 Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism Jones, Karen L. Pride, Michael C. Edmiston, Elizabeth Yang, Mu Silverman, Jill L. Crawley, Jacqueline N. Van de Water, Judy Mol Psychiatry Article Immune dysregulation has been noted consistently in individuals with autism spectrum disorder (ASD) and their families, including the presence of autoantibodies reactive to fetal brain proteins in nearly a quarter of mothers of children with ASD versus less than 1% in mothers of typically developing children. Our lab recently identified the peptide epitope sequences on seven antigenic proteins targeted by these maternal autoantibodies. Through immunization with these peptide epitopes, we have successfully created an endogenous, antigen-driven mouse model that ensures a constant exposure to the salient autoantibodies throughout gestation in C57BL/6J mice. This exposure more naturally mimics what is observed in mothers of children with ASD. Male and female offspring were tested using a comprehensive sequence of behavioral assays as well as measures of health and development highly relevant to ASD. We found that MAR-ASD male and female offspring had significant alterations in development and social interactions during dyadic play. Although 3-chambered social approach was not significantly different, fewer social interactions with an estrous female were noted in the adult male MAR-ASD animals, as well as reduced vocalizations emitted in response to social cues with robust repetitive self-grooming behaviors relative to saline treated controls. The generation of MAR ASD-specific epitope autoantibodies in female mice prior to breeding created a model that demonstrates for the first time that ASD-specific antigen-induced maternal autoantibodies produced alterations in a constellation of ASD-relevant behaviors. 2018-06-28 2020-11 /pmc/articles/PMC6310680/ /pubmed/29955164 http://dx.doi.org/10.1038/s41380-018-0126-1 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Jones, Karen L.
Pride, Michael C.
Edmiston, Elizabeth
Yang, Mu
Silverman, Jill L.
Crawley, Jacqueline N.
Van de Water, Judy
Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism
title Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism
title_full Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism
title_fullStr Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism
title_full_unstemmed Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism
title_short Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism
title_sort autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310680/
https://www.ncbi.nlm.nih.gov/pubmed/29955164
http://dx.doi.org/10.1038/s41380-018-0126-1
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