4.7 Article

Autoantibody profiling of monoamine oxidase A knockout mice, an autism spectrum disorder model

Journal

BRAIN BEHAVIOR AND IMMUNITY
Volume 107, Issue -, Pages 193-200

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2022.10.001

Keywords

Monoamine oxidase A (MAO A); MAO A knockout mice; Autism spectrum disorder (ASD); Serotonin; Antibody profiling; Human proteome microarrays; Serology

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The MAO A knockout mouse serves as a valuable model for studying neurological and behavioral impairments in ASD. This study profiled the serum antibodies of wild-type and MAO A knockout mice using high-density proteome microarray, and identified distinct autoantibody signatures. The up-regulated autoantibodies targeted brain tissues, while the down-regulated autoantibodies were enriched in sex organs. These identified autoantibodies provide insights into the pathological mechanisms of ASD and potential biomarkers for translational research.
Monoamine oxidase A (MAO A) is the critical enzyme to degrade serotonin in the brain and the knockout mouse exhibits hyperserotonemia and abnormalities that are observed in autism spectrum disorder (ASD). Thus, the MAO A knockout mouse is a valuable model for studying neurological and behavioral impairments in ASD. Based on the immune dysfunction hypothesis, dysregulated humoral immunity may cause neurological impairments. To address this hypothesis, we use high-density proteome microarray to profile the serum antibodies in both wild-type and MAO A knockout mice. The distingue autoantibody signatures were observed in the MAO A knockout and wild-type controls and showed 165 up-regulated and 232 down-regulated autoantibodies. The up -regulated autoantibodies were prone to target brain tissues while down-regulated ones were enriched in sex organs. The identified autoantibodies help bridge the gap between ASD mouse models and humoral immunity, not only yielding insights into the pathological mechanisms but also providing potential biomarkers for trans-lational research in ASD.

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