Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism.
Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism.
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DOI：
10.1038/s41380-018-0126-1
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发表时间：
2020-11
影响因子：
11
通讯作者：
Van de Water J
中科院分区：
文献类型：
--
作者：
Jones KL;Pride MC;Edmiston E;Yang M;Silverman JL;Crawley JN;Van de Water J
自闭症谱系障碍 (ASD) 患者及其家人一直存在免疫失调现象，包括近四分之一的自闭症儿童母亲体内存在对胎儿脑蛋白有反应的自身抗体，而正常发育儿童的母亲中这一比例不到 1%。我们的实验室最近鉴定了这些母体自身抗体靶向的七种抗原蛋白上的肽表位序列。通过使用这些肽表位进行免疫，我们成功创建了内源性抗原驱动的小鼠模型，确保 C57BL/6J 小鼠在整个妊娠期间持续暴露于显着的自身抗体。这种暴露更自然地模仿了自闭症谱系障碍儿童的母亲中观察到的情况。使用一系列全面的行为分析以及与自闭症谱系障碍高度相关的健康和发育指标对雄性和雌性后代进行了测试。我们发现，MAR-ASD 男性和女性后代在二元游戏期间在发育和社交互动方面发生了显着变化。尽管三腔室社交方法没有显着差异，但与生理盐水处理的对照组相比，成年雄性 MAR-ASD 动物与发情雌性的社交互动较少，并且响应社交线索而发出的声音减少，并具有强烈的重复性自我梳理行为。 MAR 在繁殖前在雌性小鼠中产生 ASD 特异性表位自身抗体，创建了一个模型，首次证明 ASD 特异性抗原诱导的母体自身抗体产生了一系列 ASD 相关行为的改变。
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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DOI：
10.1111/j.1601-183x.2012.00849.x
发表时间：
2012-11
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
Ey E;Yang M;Katz AM;Woldeyohannes L;Silverman JL;Leblond CS;Faure P;Torquet N;Le Sourd AM;Bourgeron T;Crawley JN
通讯作者：
Crawley JN
影响因子：
6.8
作者：
Braunschweig D;Krakowiak P;Duncanson P;Boyce R;Hansen RL;Ashwood P;Hertz-Picciotto I;Pessah IN;Van de Water J
通讯作者：
Van de Water J
影响因子：
4.7
作者：
Chadman, Kathryn K.;Gong, Shiaoching;Crawley, Jacqueline N.
通讯作者：
Crawley, Jacqueline N.
DOI：
10.1097/dbp.0000000000000351
发表时间：
2016-10
期刊：
Journal of developmental and behavioral pediatrics : JDBP
影响因子：
--
作者：
Beversdorf DQ;MISSOURI AUTISM SUMMIT CONSORTIUM
通讯作者：
MISSOURI AUTISM SUMMIT CONSORTIUM
影响因子：
3.7
作者：
Ariza J;Hurtado J;Rogers H;Ikeda R;Dill M;Steward C;Creary D;Van de Water J;Martínez-Cerdeño V
通讯作者：
Martínez-Cerdeño V