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

Karen L. Jones, Michael C. Pride, Elizabeth Edmiston, Mu Yang, Jill L Silverman, Jacqueline Crawley, Judith A Van de Water

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 <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.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalMolecular Psychiatry
DOIs
StateAccepted/In press - Jun 28 2018

Fingerprint

Autistic Disorder
Autoantibodies
Mothers
Antigens
Epitopes
Interpersonal Relations
Fetal Proteins
Autism Spectrum Disorder
Grooming
Peptides
Inbred C57BL Mouse
Breeding
Cues
Immunization
Pregnancy
Health
Brain

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

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; Van de Water, Judith A.

In: Molecular Psychiatry, 28.06.2018, p. 1-16.

Research output: Contribution to journalArticle

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