Caspr2-reactive antibody cloned from a mother of an ASD child mediates an ASD-like phenotype in mice.
Mol Psychiatry
; 21(12): 1663-1671, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27698429
ABSTRACT
Autism spectrum disorder (ASD) occurs in 1 in 68 births, preferentially affecting males. It encompasses a group of neurodevelopmental abnormalities characterized by impaired social interaction and communication, stereotypic behaviors and motor dysfunction. Although recent advances implicate maternal brain-reactive antibodies in a causative role in ASD, a definitive assessment of their pathogenic potential requires cloning of such antibodies. Here, we describe the isolation and characterization of monoclonal brain-reactive antibodies from blood of women with brain-reactive serology and a child with ASD. We further demonstrate that male but not female mice exposed in utero to the C6 monoclonal antibody, binding to contactin-associated protein-like 2 (Caspr2), display abnormal cortical development, decreased dendritic complexity of excitatory neurons and reduced numbers of inhibitory neurons in the hippocampus, as well as impairments in sociability, flexible learning and repetitive behavior. Anti-Caspr2 antibodies are frequent in women with brain-reactive serology and a child with ASD. Together these studies provide a methodology for obtaining monclonal brain-reactive antibodies from blood B cells, demonstrate that ASD can result from in utero exposure to maternal brain-reactive antibodies of single specificity and point toward the exciting possibility of prognostic and protective strategies.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Membrana
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Adult
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Animals
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Female
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Humans
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Middle aged
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Pregnancy
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article